Journal of Respiration

Observational studies suggest a comorbid link between asthma and endometriosis, but the evidence remains limited and inconsistent. This study presents a meta-analysis examining this association. A comprehensive search of literature databases was conducted through August 2024. Prevalence rates and odds ratios (ORs) were calculated to assess the relationship between asthma and endometriosis. For the prevalence analysis, sixteen studies, including 54,856 endometriosis cases and 300,613 controls, were included. The analysis yielded a prevalence of asthma in endometriosis patients of 14.9% (95% CI [10.3, 19.6], p < 0.001), with high heterogeneity (I² = 99.9%). In the control group, asthma prevalence was 9.1% (95% CI [6.5, 11.6], p < 0.001, I² = 99.9%). For the odds ratio (OR) analysis, twelve studies, including 295,845 endometriosis cases and 28,030,081 controls, were included. The meta-analysis demonstrated a significant association between asthma and endometriosis with an OR of 1.59 (95% CI [1.22, 2.07], p = 0.0007, I² = 100%). Subgroup analyses stratified by study region and study type were also conducted. This meta-analysis suggests a significant association between asthma and endometriosis, indicating that common factors underlying these chronic inflammatory diseases may contribute to this comorbidity. The findings support the biological plausibility of this association. Full article

Background/Objectives: Mask-wearing-induced discomfort often leads to unconscious loosening of the mask to relieve the discomfort, thereby compromising protective efficacy. This study investigated how leakage flows affect mask-associated thermoregulation and vapor trapping to inform better mask designs. An integrated ambience–mask–face–airway model with various mask-wearing misfits was developed. Methods: The transient warming/cooling effects, thermal buoyancy force, tissue heat generation, vapor phase change, and fluid/heat/mass transfer through a porous medium were considered in this model, which was validated using Schlieren imaging, a thermal camera, and velocity/temperature measurements. Leakages from the top and side of the mask were analyzed in comparison to a no-leak scenario under cyclic respiration conditions. Results: A significant inverse relationship was observed between mask leakage and facial temperature/humidity. An equivalent impact from buoyancy forces and exhalation flow inertia was observed both experimentally and numerically, indicating a delicate balance between natural convection and forced convection, which is sensitive to leakage flows and critical in thermo-humidity regulation. For a given gap, the leakage fraction was not constant within one breathing cycle but constantly increased during exhalation. Persistently higher temperatures were found in the nose region throughout the breathing cycle in a sealed mask and were mitigated during inhalation when gaps were present. Vapor condensation occurred within the mask medium during exhalation in all mask-wearing cases. Conclusions: The thermal and vapor temporal variation profiles were sensitive to the location of the gap, highlighting the feasibility of leveraging temperature and relative humidity to test mask fit and quantify leakage fraction. Full article

Tuberculosis (TB) is a leading cause of death from a single infectious agent in humans. The morbidity and mortality due to TB are further worsened by co-existing health conditions and the emergence of drug-resistant (DR-TB) cases. The WHO has declared TB as a global emergency and endorsed global efforts to improve diagnosis, and treatment while reducing the catastrophic cost in an EndTB strategy in 2013, with a vision to create a TB-free world. In the past decade, molecular diagnostic tools, such as nucleic acid amplification technologies (NAATs), have replaced the conventional smear microscopy of TB, thus offering better bacteriological confirmation and case detection along with drug resistance in pulmonary and extrapulmonary samples. Follow-on testing using a more advanced targeted next-generation sequencing (tNGS) system has improved the diagnosis of cases resistant to first- and second-line anti-TB drugs, including newer ones. TB treatment has been improved with the introduction of newer drugs including an all-oral regimen for DR-TB, thereby improving patient compliance. Improved TB prevention is achieved through the broadening of BCG vaccination as well as preventive therapy for asymptomatic, latent TB (LTBI) cases, which, otherwise, can reactivate to symptomatic disease. However, the recent goal of the WHO’s EndTB-2035 strategy has been met with significant challenges in the areas of implementing improved diagnosis and treatment modalities in resource-limited TB endemic countries. The complexity of global TB management is confounded by malnutrition, comorbidities with other infectious and non-infectious diseases, and the socio-economic landscape of vulnerable populations. Political commitment to universal health coverage (UHC), including service coverage and reduction in catastrophic cost, are some of the essential components that need to be addressed to achieve the EndTB strategy. In this perspective, we have highlighted the intricacies of global TB management and summarized some of the key challenges that may keep the WHO’s EndTB-2035 strategy on the fence. Full article

ChatGPT (Chat-Generative Pre-trained Transformer) is an accessible and innovative tool for obtaining healthcare information. This study evaluates the quality and reliability of information provided by ChatGPT 4.0^® regarding Obstructive Sleep Apnea (OSA), comparing it with responses from sleep medicine specialists. Thirty frequently asked questions about OSA were posed to ChatGPT 4.0^® and two expert physicians. Responses from both sources (V1: AI and V2: Medical Experts) were blindly evaluated by a panel of six specialists using a five-point Likert scale across precision, relevance, and depth dimensions. The AI-generated responses (V1) achieved a slightly higher overall score compared to those from medical experts (V2), although the difference was not statistically significant (p > 0.08). These results suggest that both sources offer comparable quality and content. Additionally, ChatGPT’s responses were clear and easily understandable, providing an accessible explanation of OSA pathology. Full article

Background/Objectives: Since the discovery of oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusions in colorectal cancer in 1986, their understanding has evolved, particularly in non-small-cell lung cancer (NSCLC) over the past five years. NTRK rearrangements, involving NTRK1, NTRK2, and NTRK3, drive tumorigenesis and have been identified in various adult and pediatric cancers, with over 80 different fusion variants in several type of cancers. Detecting these rearrangements is crucial for targeted therapy strategies. The aim of this study is detect, compare and analyse these mutations in NSCLC patients of a cohort of 482 cases from Karolinska University Hospital. Methods: We conducted an initial screening using pan-TRK immunohistochemistry (IHC) to analyze the material. Positive cases were further examined through whole-exome sequencing (WES) with next-generation sequencing (NGS) to confirm the presence of fusions. Additionally, to deepen our understanding, we utilized Ingenuity Pathway Analysis (IPA) software, an artificial intelligence-driven technology, to explore the molecular pathways involved in lung cancer. Results: TRK overexpression was detected in 4.56% of cases via IHC. Among 15 pan-TRK-positive cases, WES confirmed fusions in 3, revealing a higher prevalence of NTRK1 (6.6%) and NTRK2 (13.3%) fusions, while no NTRK3 fusions were observed. Conclusions: Our findings confirm the low prevalence of these neoplasms as well as the need for a molecular test to confirm rearrangements or other potentially treatable mutations and raise other questions regarding their clinical use. However, there is an acceptable correlation between pan-TRK IHC and NTRK mutations, but not enough to determine NTRK fusions. Full article

Background: There is a limitation in understanding complete cardiopulmonary function during moments of exhaustive exercise due to invasive measurement techniques. We asked how cardiopulmonary function is perturbed during times of exercise in different age cohorts: 6–11 and 11–18. We sought to broadly analyze how age and oxidative stress during exercise differ across age cohorts. Methods: We present a whole-body physiology model that connects the nervous, cardiovascular, respiratory, and oxygen transport and binding systems. We connect these models using a lumped parameter representation of the cardiovascular and respiratory systems. Results: we observe distinct age-related difference in physiological response to exercise. These responses consist of respiratory, cardiovascular, and nervous system perturbations that are distinct across these age groups. Full article

Self-Expanding Metallic (SEM) Y stents are a newer form of stent that is gaining popularity outside the USA, but still has limited data, especially in a community medicine setting. This study analyzed efficacy and complication rates in 14 patients who had a SEM Y stent placed between August 2022 and June 2024 at Harris Methodist Hospital in Fort Worth, Texas for either central airway obstruction (CAO) or fistulae. Of the 14 patients, 11 were requiring supplemental oxygen or mechanical ventilation prior to stent placement. Post-stenting 42.9% had decreased oxygen requirements, 21.4% unchanged, 14.3% increased, and 21.4% remained on room air. Complications included mucus plugging (42.9%), infection (35.7%), and granulation tissue (14.3%). There was no statistically significant correlation between gender/age and complications (p = 0.879/0.490, respectively). Complication rates were similar when compared to silicone Y stents based on literature review. In conclusion, SEM Y stents are a safe and effective alternative stent intended for palliative treatment with similar success and complications that can be easily and effectively implemented in a community hospital, with the added benefit of being able to be placed with flexible bronchoscopy. Full article

The management of malignant pleural effusions (MPEs) has developed hugely since the publication of the management of an MPE: British Thoracic Society (BTS) Pleural Disease Guideline 2010. The presence of an MPE reflects advanced or metastatic disease (excluding malignant pleural mesothelioma) and thus the management of MPE often focuses on symptomatic relief of symptoms and improving quality of life. We provide a review of the 2023 BTS guidance in relation to malignant pleural effusions and specific points on imaging and systemic anti-cancer treatment by concentrating on a hypothetical patient vignette. Full article

Background: Asthma is a respiratory disorder influenced by genetic and environmental factors. The rs7216389 polymorphism in the gasdermin B (GSDMB) gene on chromosome 17q21 has been implicated in asthma susceptibility with conflicting results. This meta-analysis aims to bring forward new findings on the association between this polymorphism and asthma across diverse populations and its potential as a genetic marker for asthma risk. Methods: A systematic review and meta-analysis were conducted through March 2024, and odd ratios were calculated. Results: The meta-analysis included 22 studies with a total of 9012 asthma patients and 11,657 controls. The results show an OR = 1.24, 95% CI [1.13, 1.37], p < 0.00001. Subgroup analyses stratified by age and ethnicity between asthma patients with T alleles vs. C alleles demonstrated an association between having the T allele and asthma susceptibility across Asian, Caucasian, and American minorities, but not among Arabs. Young asthma patients with the dominant allele (T) showed higher asthma risk than those with C allele or heterozygote TC, and to a higher extent than for adults. Conclusions: This meta-analysis indicates the importance of genetic factors in asthma in certain ethnicities and underscores the potential utility of the rs7216389 polymorphism as a genetic marker for asthma risk assessment. Full article

Patients with a mesothelioma diagnosis often have relatively sedentary lifestyles and low physical activity. Reducing sedentary behaviour and being more active could be beneficial. A greater understanding of the factors associated with physical activity is needed to inform the development of interventions. Semi-structured interviews with patients with mesothelioma and informal carers were performed and analysed thematically. Three themes were generated: (1) the impact of disease burden and physical and psychological symptoms, (2) the psychosocial consequences and benefits of physical activity and (3) unpredictability and maintaining control. Participants had become increasingly sedentary during diagnosis and while undergoing treatment. Symptoms were key factors contributing to these reductions. Being less active reduced social connectedness and impacted psychological well-being. Some participants had lost confidence in being active and were worried about the potential negative consequences of doing more. Being able to walk was a priority, and they felt hopeful about increasing this in the future, but this depended on optimisation of symptoms. Clear guidance from healthcare professionals was needed to support engagement in physical activity. Declines in physical activity can have meaningful consequences for patients. Optimisation of symptoms is important to devise strategies to support patients with physical activity. Along with encouragement from healthcare professionals. Full article

Extramedullary myeloma with pulmonary and pleural involvement is rare and can present in different ways. Here we present two cases of extramedullary pulmonary disease in relapsed/refractory multiple myeloma. Background: Multiple myeloma remains an incurable disease with unmet need for new treatments for high-risk disease such as extramedullary plasmacytoma. Relapses can occur at different stages due to the heterogeneity of the disease. While relapsed/refractory disease can be challenging to treat, progression can also lead to extramedullary disease which indicates an aggressive form with poor outcomes. Pulmonary extramedullary disease can present in various ways, such as a lung mass, parenchymal infiltrates, pleural mass, or pleural effusion. Objective: Our case series highlights two different presentations of pulmonary extramedullary disease and a review of the treatment of relapsed/refractory myeloma. Our patients highlight the progression of their multiple myeloma due to the aggressive nature of their extramedullary disease. Their cases emphasize the importance of new targeted treatments to treat extramedullary disease and penta-refractory disease as there is no currently accepted standard regimen for this difficult to treat condition. Full article

This paper presents a formative assessment for the implementation of mobile portable chest X-ray (PDX) machines for tuberculosis (TB) contact tracing in the Oyo and Osun states, Nigeria. This descriptive qualitative study was carried out in eight local government areas, and 24 focus group discussions and 30 key informant interviews were conducted using a four-stage sampling technique to select participants. Validated transcribed notes were entered and analyzed using Nvivo. The respondents’ ages ranged from 17 to 85 years, with a mean age of 42.08 ± 14.9 years, and 4.0% had a postgraduate degree. The majority of government officials stated that deploying the PDX machine for screening at the community level is the best means for implementation because it will offer a level of proximity convenience to the TB contacts and assuage concerns about the cost of transportation to the health facility. In addition, it was suggested that TB community screening should be carried out with screening for other health conditions such as high blood pressure and diabetes. This portable X-ray machine intervention, therefore, should be implemented at the community level for contact tracing to allow more TB contacts living with the index patient to be screened without proximity and transportation constraints. Full article

Patients with metastatic breast cancer often have respiratory symptoms due to various causes. Trastuzumab is a drug used in the treatment of HER2/neu over-expressing breast cancer patients. Organising pneumonia is a type of idiopathic interstitial pneumonia that mimics infection or progressive disease and can be difficult to diagnose in the setting of malignancy. Making a correct diagnosis is of extreme importance since any delay in the treatment can result in significant adverse patient outcome. Here, we have described a case of organising pneumonia associated with the use of trastuzumab in metastatic breast cancer patients. On the basis of clinical data, including findings such as a decreased PaO2 level and findings on chest CT scan, these patients were diagnosed with drug-induced organising pneumonia. Although it is a rare adverse event associated with trastuzumab, it may cause rapid deterioration without preceding symptoms; hence, even though it is very rare, with an incidence of less than 2%, it is still crucial to intervene so as to prevent the occurrence of such an unfavourable outcome by means of close observation and early diagnosis along with an early withdrawal of the drug and an immediate commencement of corticosteroid therapy. Full article

RAGE (receptor for advanced glycation end-products) represents a class of multi-ligand pattern recognition receptors highly expressed in the vertebrate lung. Our previous work demonstrated unique patterns of RAGE expression in the developing murine lung and regulation by key transcription factors including NKX2.1 and FoxA2. The current investigation employed conditional lung-specific upregulation via a TetOn transgenic mouse model (RAGE TG) and nontransgenic controls. RAGE expression was induced in RAGE TG mice throughout gestation (embryonic day, E0-E18.5) or from E15.5-E18.5 and compared to age-matched controls. High-resolution respirometry was used to assess mitochondrial respiration and context was provided by quantifying ATP and reactive oxygen species (ROS) generation. Lung lysates were also screened by immunoblotting for MAPK/PI3K signaling intermediates. RAGE upregulation increased mitochondrial oxygen consumption in the E0-E18.5 and E15.5-E18.5 groups compared to controls. RAGE TG mice also had increased ATP concentrations, which persisted even after controlling for oxygen consumption. In contrast, ROS generation was diminished in RAGE TG animals compared to controls. Lastly, in both RAGE TG groups, pERK and pp38 were significantly decreased, whereas pAKT was significantly elevated, suggesting that RAGE signaling is likely perpetuated via pAKT pathways. Together, these data demonstrate that despite lung hypoplasia in RAGE TG mice, the remaining tissue experiences a favorable shift in mitochondrial bioenergetics without excessive redox assault and a preference for AKT signaling over ERK or p38. Full article

Lung cancer, a major global cause of cancer-related deaths, demands continual advancements in diagnostic methodologies. This review delves into the transformative role of Robotic-Assisted Bronchoscopy (RAB) in redefining lung cancer diagnostics. As lung cancer screenings intensify, leading to a surge in pulmonary nodule diagnoses, navigational bronchoscopy, notably electromagnetic navigational bronchoscopy (ENB), faces persistent limitations. Examining key RAB platforms—Monarch™, Ion™ and the Galaxy System™—reveals their distinctive features, with RAB demonstrating superior diagnostic yields over traditional biopsy methods. However, challenges include CT-to-body divergence (CBCT) and divergent findings in diagnostic yield studies and a lack of head-to-head comparisons with non-RAB modalities. Future directions should explore RAB’s potential therapeutic applications, shaping the landscape of both diagnostics and therapeutics in lung cancer management. Full article

Pleural infection, including empyema, continues to have a high morbidity. A deep understanding of the pathobiology and appropriate medical management is crucial to avoid complications and progression to the need for surgery. Over the last several decades, we have learned much about the pathophysiology, microbiology, and epidemiology of pleural infections. Management has changed considerably over the years with more recent clinical practices favoring minimally invasive interventions over surgery. Here we discuss in detail the pathophysiology of parapneumonic effusions as they progress from uncomplicated parapneumonic effusions to empyema and how this relates to their diagnosis and management. We review the microbiology and how it relates to recommended empiric antibiotic regimens. As intrapleural fibrinolytic therapy has become the cornerstone of management, we outline the literature on this topic dating back decades up to the most recent clinical trials and give our recommendations for management based on the literature. Full article

Introduction: Those with cardiac sarcoidosis (CS) are at risk of sudden cardiac death (SCD), which may be prevented using an implantable cardioverter–defibrillator (ICD). There are limited data available that follow the post-procedural outcomes of patients with cardiac sarcoidosis (CS) who have had an ICD implanted. Areas Covered: This review highlights studies that focused on both appropriate and inappropriate therapies in those with an ICD, as well as device complications in this group. There were several variables, including age, sex, ventricular characteristics, and findings on cardiac imaging that were investigated and discussed as influencing factors in predicting appropriate and inappropriate therapies. Conclusions: Adverse events in those with an ICD and CS have been minimally reported in the literature. Individuals diagnosed with CS are at high risk of ventricular arrhythmia, with comparable rates of appropriate therapy but with a higher incidence of side effects and inappropriate therapy. The younger average age of CS patients in comparison to other ICD cohorts warrants the need for further, large-scale, prospective trials with periodic interim follow-ups focused on those with this condition. Full article

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS. Full article