Disseminated MDR-TB missed in a patient treated with TNF inhibitor.

A previously healthy man developed pulmonary symptoms 2 weeks after starting treatment with a tumour necrosis factor (TNF) inhibitor. A negative interferon-gamma release assay (IGRA) test was obtained prior to TNF inhibitor exposure, without consideration of the fact that the patient was already immunosuppressed and had a previous positive IGRA test 17 months earlier. The patient was treated for pneumonia twice but did not achieve remission. His physical health progressively deteriorated over the following months. Malignancy was suspected but not found. Eight months after the onset of symptoms, Mycobacterium tuberculosis was found in samples from mediastinal lymph nodes, and the patient was diagnosed with multidrug-resistant tuberculosis (MDR-TB).This case illustrates the diagnostic challenge of TB, the need to raise awareness of the increased risk of TB in patients treated with TNF inhibitors and the need to increase knowledge regarding the effect of immunosuppressive agents on IGRA tests.

Quantitative measurement of the flow depending nasal valve function by elastography with electro-optical distance sensors. A pilot study.

Nasal valve function depends on the intensity of the inspiratory nasal airflow, the geometry of the nasal entrance and the mechanical properties of the lateral nasal wall. It is desirable to obtain objective information on the relation between flow and valve movement. In this study, the deflection of the lateral nasal wall and the inspiratory flow were measured on 30 healthy volunteers, aged 18 to 82 without a history of severe trauma or nasal surgery. Electro-optical distance sensors were housed under a full-face protective mask attached to an analogue inspiratory flowmeter. The mean values for normal breathing were assessed at 675 [cm3/s] for the bilateral flow and -0.57 mm for the total movement. With forced breathing, the mean values for the flow of both nostrils were found to be 1434 cm3/s and for the total movement -1.21 mm. Statistically significant differences between normal and forced breathing were found in all participants and in both sexes, but no significant correlation by age. Electro-optical distance measurement, representing a novel technical way for the 'elastography' of the nasal valve should be added to advanced 4-phase-rhinomanometers.

Mechanisms of Mechanical Stimulation in the Development of Respiratory System Diseases.

During respiration, mechanical stress can initiate biological responses that impact the respiratory system. Mechanical stress plays a crucial role in the development of the respiratory system. However, pathological mechanical stress can impact the onset and progression of respiratory diseases by influencing the extracellular matrix and cell transduction processes. In this article, we explore the mechanisms by which mechanical forces communicate with and influence cells. We outline the basic knowledge of respiratory mechanics, elucidating the important role of mechanical stimulation in influencing respiratory system development and differentiation from a microscopic perspective. We also explore the potential mechanisms of mechanical transduction in the pathogenesis and development of respiratory diseases such as asthma, lung injury, pulmonary fibrosis, and lung cancer. Finally, we look forward to new research directions in cellular mechanotransduction, aiming to provide fresh insights for future therapeutic research on respiratory diseases.

Management of a rare case of lymphangioleiomyomatosis complicated by recurrent pneumothorax.

A female of reproductive age presents to the emergency department with progressive dyspnoea due to pneumothorax. She has a history of lymphangioleiomyomatosis (LAM) diagnosed by lung biopsy 15 years ago following incidental finding of pneumothorax. Despite various procedural and medicinal treatments, she continued to have recurrent pneumothorax, with three hospital admissions over the preceding 3 months. LAM is a rare cystic lung disease affecting the lymphatic system, which most commonly affects women of childbearing age. It can be diagnosed via imaging or tissue biopsy (gold standard). Treatment can be difficult, and it often requires highly specialised care by pulmonologists and often confers significant limitations to patients' independence and quality of life. Family physicians are often part of multidisciplinary team to provide care to patients with rare chronic conditions.

Respiratory system compliance during anesthesia induction and postoperative mechanical ventilation needs: An observational study.

Background and Aims: Respiratory system compliance (Crs) is a simple indicator of lung flexibility. However, it remains unclear whether a low Crs during anesthesia induction (iCrs) is associated with an increased risk of postoperative mechanical ventilation. Methods: This retrospective observational study was conducted using a local database. All mechanically ventilated postoperative ICU patients were included in this study. The duration of postoperative mechanical ventilation, length of hospital stay, and in-hospital mortality were compared between the low iCrs group (<25% of distribution) and the normal iCrs group. Results: A total of 315 patients were classified into the low iCrs (<39 mL/cmH2O) group (n = 78) or the normal iCrs group (n = 237). Low iCrs was associated with a higher chance of mechanical ventilation in 28 days (log-rank test, p < 0.001). The duration of hospital stay was similar. Multivariate analysis showed that in-hospital mortality was higher in the low iCrs group than in the normal iCrs group (adjusted odds ratio, 6.04 [1.13, 32.26]; p = 0.04). Conclusion: Low iCrs was associated with an increased risk of requiring postoperative mechanical ventilation. An additional result of poor survival related to low iCrs may require further study.

Anti-inflammatory and antioxidant activity of high concentrations of hydrogen in the lung diseases: a systematic review and meta-analysis.

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.

Respiratory system: Highly exposed yet under-reported organ in pyrethrin and pyrethroid toxicity.

Pyrethrin and pyrethroid are a relatively new class of pesticides with potent insecticidal properties. Pyrethrins are naturally occurring pesticides obtained from the Chrysanthemum cinerariaefolium flower, while pyrethroids are their synthetic derivatives. They are widely used as the insecticides of choice in agriculture, veterinary medicine, public health programs, and household activities. Pyrethrin, being a broad-spectrum insecticide kills a wide range of pests, while pyrethroids last longer in the environment owing to low susceptibility to sunlight, and greater stability and efficacy than parent molecules. Humans can be exposed through inhalation, ingestion, and dermal routes. Indoor usage of an insecticide poses a serious risk to human health, especially to women, children, and stay-at-home people. Although pyrethrin and pyrethroid are generally considered safe, sustained skin or inhalation exposure or direct contact with open wounds results in higher toxicity to mammals. There is a paucity of data on the impact of pyrethrin and pyrethroid on overall pulmonary health. The respiratory system, from the nose, nasal passages, airways, and bronchi to the pulmonary alveoli, is vulnerable to environmental contaminants such as pesticides because of its anatomical location as well as being a highly blood profused organ. Under and over-functioning of the respiratory system triggers diverse pathologies such as serious infections, allergies, asthma, metastatic malignancies, and auto-immune conditions. While the association between workplace-related pesticide exposures and respiratory diseases and symptoms is well documented, it is important to understand the adverse health impact of pyrethrin and pyrethroid on the general population for awareness and also for better regulation and implementation of the law.

Roles and mechanisms of circular RNA in respiratory system cancers.

Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5'-ended cap and 3'-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression.

Transient haemoptysis after taking sildenafil.

We report a case of a man in his 70s who developed haemoptysis 3 days after commencing sildenafil. Before postulating a potential connection between sildenafil use and haemoptysis, it is important to rule out potential other causative factors and comorbidities. The patient suffers from multiple medical conditions and takes various medications. On examination, no abnormalities were discovered. There were no recent significant changes in his bloodwork. Cessation of sildenafil coincided with spontaneous symptom resolution. Chest CT was performed, and no abnormalities were reported. Pseudohaemoptysis or malignancy may be the main differential diagnoses of haemoptysis in elderly patients with multiple comorbidities. Concurrent anticoagulation of the patient may predispose to haemoptysis and is likely to be of greater clinical concern.

Paradoxical development of Kimura's disease in a patient treated with mepolizumab for bronchial asthma.

A male patient in his early 30s was diagnosed with bronchial asthma 3 years previously. He responded well to inhaled corticosteroids and long-acting beta-agonists. Approximately 18 months from the onset, the patient reported worsening symptoms. These symptoms included severe functional limitations, requiring frequent exposure to high-dose prednisolone. Mepolizumab was added to the treatment, leading to optimal control of bronchial asthma. Despite receiving seven doses of mepolizumab at monthly intervals, the patient developed cervical and postauricular lymphadenopathy and subcutaneous swelling of soft tissue. A cervical lymph node biopsy confirmed the diagnosis of Kimura disease. Following treatment with oral glucocorticoids and methotrexate, the patient experienced a complete resolution of symptoms. He has been in remission and off oral prednisolone for the last 13 months. In this case, we highlight the development of Kimura disease in a patient undergoing mepolizumab treatment.

Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.

Disease types and pathogenic mechanisms induced by PM2.5 in five human systems: An analysis using omics and human disease databases.

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

Pseudomonas and aspergillus symbiotic coinfections in a case of chronic obstructive pulmonary disease and diabetes mellitus.

Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.

Artificial sweetener and respiratory system cancer: A Mendelian randomization analysis.

BACKGROUND & AIMS: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis. METHODS: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results. RESULTS: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer. CONCLUSIONS: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.

Universal paediatric videolaryngoscopy and glottic view grading: a prospective observational study.

BACKGROUND: Although videolaryngoscopy has been proposed as a default technique for tracheal intubation in children, published evidence on universal videolaryngoscopy implementation programmes is scarce. We aimed to determine if universal, first-choice videolaryngoscopy reduces the incidence of restricted glottic views and to determine the diagnostic performance of the Cormack and Lehane classification to discriminate between easy and difficult videolaryngoscopic tracheal intubations in children. METHODS: We conducted a prospective observational study within a structured universal videolaryngoscopy implementation programme. We used C-MAC™ (Karl Storz, Tuttlingen, Germany) videolaryngoscopes in all anaesthetised children undergoing elective tracheal intubation for surgical procedures. The direct and videolaryngoscopic glottic views were classified using a six-stage grading system. RESULTS: There were 904 tracheal intubations in 809 children over a 16-month period. First attempt and overall success occurred in 607 (67%) and 903 (> 99%) tracheal intubations, respectively. Difficult videolaryngoscopic tracheal intubation occurred in 47 (5%) and airway-related adverse events in 42 (5%) tracheal intubations. Direct glottic view during laryngoscopy was restricted in 117 (13%) and the videolaryngoscopic view in 32 (4%) tracheal intubations (p < 0.001). Videolaryngoscopy improved the glottic view in 57/69 (83%) tracheal intubations where the vocal cords were only just visible, and in 44/48 (92%) where the vocal cords were not visible by direct view. The Cormack and Lehane classification discriminated poorly between easy and difficult videolaryngoscopic tracheal intubations with a mean area under the receiver operating characteristic curve of 0.68 (95%CI 0.59-0.78) for the videolaryngoscopic view compared with 0.80 (95%CI 0.73-0.87) for the direct glottic view during laryngoscopy (p = 0.005). CONCLUSIONS: Universal, first-choice videolaryngoscopy reduced substantially the incidence of restricted glottic views. The Cormack and Lehane classification was not a useful tool for grading videolaryngoscopic tracheal intubation in children.

Analysis of the effect of inert gas on alveolar/venous blood partial pressure by using the operator splitting method.

This study aims to investigate how inert gas affects the partial pressure of alveolar and venous blood using a fast and accurate operator splitting method (OSM). Unlike previous complex methods, such as the finite element method (FEM), OSM effectively separates governing equations into smaller sub-problems, facilitating a better understanding of inert gas transport and exchange between blood capillaries and surrounding tissue. The governing equations were discretized with a fully implicit finite difference method (FDM), which enables the use of larger time steps. The model employed partial differential equations, considering convection-diffusion in blood and only diffusion in tissue. The study explores the impact of initial arterial pressure, breathing frequency, blood flow velocity, solubility, and diffusivity on the partial pressure of inert gas in blood and tissue. Additionally, the effects of anesthetic inert gas and oxygen on venous blood partial pressure were analyzed. Simulation results demonstrate that the high solubility and diffusivity of anesthetic inert gas lead to its prolonged presence in blood and tissue, resulting in lower partial pressure in venous blood. These findings enhance our understanding of inert gas interaction with alveolar/venous blood, with potential implications for medical diagnostics and therapies.

Pulmonary renal syndrome secondary to malignant hypertension.

A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.

Analysis of particulate matter-induced alteration of genes and related signaling pathways in the respiratory system.

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation.