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Advances in Clinical and Experimental... May 2018Nowadays, lung cancer is a leading cause of death in both men and women worldwide. There is no clear explanation for its mortality rate. However, it is already known... (Review)
Review
Nowadays, lung cancer is a leading cause of death in both men and women worldwide. There is no clear explanation for its mortality rate. However, it is already known that genetic and environmental factors as well as oncological treatment are involved. As the incidence of lung cancer soars, the number of patients diagnosed with multiple primary lung cancers (MPLC) is also rising. While differentiating between MPLC and intrapulmonary metastasis of lung cancer is important for treatment strategy and prognosis, it is also quite complicated, particularly in the cases with similar histologies. It is also important not to delay the diagnosis. The aim of this paper was to discuss MPLC in general, and the differentiation between MPLC and intrapulmonary lung cancer metastasis in particular. Based on a review of statistical data and the current literature, we discuss the diagnostic criteria and the molecular, genetic and radiographic methods used to distinguish between MPLC and intrapulmonary metastases.
Topics: Biomarkers, Tumor; Female; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Multiple Primary
PubMed: 29790681
DOI: 10.17219/acem/68631 -
The European Respiratory Journal Aug 2021https://bit.ly/3whQVqd
https://bit.ly/3whQVqd
Topics: Humans; Interleukin-6
PubMed: 34210792
DOI: 10.1183/13993003.01292-2021 -
Frontiers in Physiology 2022Known to have affected around 340 million people across the world in 2018, asthma is a prevalent chronic inflammatory disease of the airways. The symptoms such as... (Review)
Review
Known to have affected around 340 million people across the world in 2018, asthma is a prevalent chronic inflammatory disease of the airways. The symptoms such as wheezing, dyspnea, chest tightness, and cough reflect episodes of reversible airway obstruction. Asthma is a heterogeneous disease that varies in clinical presentation, severity, and pathobiology, but consistently features airway hyperresponsiveness (AHR)-excessive airway narrowing due to an exaggerated response of the airways to various stimuli. Airway smooth muscle (ASM) is the major effector of exaggerated airway narrowing and AHR and many factors may contribute to its altered function in asthma. These include genetic predispositions, early life exposure to viruses, pollutants and allergens that lead to chronic exposure to inflammatory cells and mediators, altered innervation, airway structural cell remodeling, and airway mechanical stress. Early studies aiming to address the dysfunctional nature of ASM in the etiology and pathogenesis of asthma have been inconclusive due to the methodological limitations in assessing the intrapulmonary airways, the site of asthma. The study of the trachealis, although convenient, has been misleading as it has shown no alterations in asthma and it is not as exposed to inflammatory cells as intrapulmonary ASM. Furthermore, the cartilage rings offer protection against stress and strain of repeated contractions. More recent strategies that allow for the isolation of viable intrapulmonary ASM tissue reveal significant mechanical differences between asthmatic and non-asthmatic tissues. This review will thus summarize the latest techniques used to study ASM mechanics within its environment and in isolation, identify the potential causes of the discrepancy between the ASM of the extra- and intrapulmonary airways, and address future directions that may lead to an improved understanding of ASM hypercontractility in asthma.
PubMed: 36277199
DOI: 10.3389/fphys.2022.993406 -
Archivos de Cardiologia de Mexico Apr 2022Platypnea orthodeoxia syndrome (POS) is a clinical entity described in the middle of the last century. It is characterized by dyspnea and hypoxemia triggered by standing... (Review)
Review
Platypnea orthodeoxia syndrome (POS) is a clinical entity described in the middle of the last century. It is characterized by dyspnea and hypoxemia triggered by standing and relieved with recumbency. The diagnosis is predominately clinical. The degree of hypoxemia is variable; however, the diagnostic criteria include the decrease in arterial oxygen pressure more than 4 mmHg or oxygen saturation more than 5%. Even though many diseases cause this syndrome, there are only two responsible mechanisms, intracardiac, and intrapulmonary shunts. The coexistence of diverse structural and physiological abnormalities joined to gravitational forces that induce blood shunt after standing is crucial in each mechanism. The intracardiac mechanism is characterized by right to left blood shunt through atrial septal communications and, the right atrium pressure could be normal or increased. In addition, some patients have one or more coexistent aortic, spinal, or intracardiac alterations. The intrapulmonary mechanism is less frequent and is caused by parenchymal or vascular pathologies. Transthoracic echocardiogram is the first diagnostic modality; however, understanding the pathophysiology is the key for a rational diagnostic approach and subsequent diagnostic studies. Treatment is possible and effective in the majority of intracardiac mechanisms and some intrapulmonary. This review focuses on the pathophysiologic mechanisms of POS and their diagnostic workup.
Topics: Dyspnea; Foramen Ovale, Patent; Humans; Hypoxia; Posture; Syndrome
PubMed: 34428199
DOI: 10.24875/ACM.21000171 -
EBioMedicine Apr 2023In the era of histopathology-based diagnosis, the discrimination between multiple lung cancers (MLCs) poses significant uncertainties and has thus become a clinical... (Review)
Review
In the era of histopathology-based diagnosis, the discrimination between multiple lung cancers (MLCs) poses significant uncertainties and has thus become a clinical dilemma. However, recent significant advances and increased application of molecular technologies in clonal relatedness assessment have led to more precision in distinguishing between multiple primary lung cancers (MPLCs) and intrapulmonary metastasis (IPMs). This review summarizes recent advances in the molecular identification of MLCs and compares various methods based on somatic mutations, chromosome alterations, microRNAs, and tumor microenvironment markers. The paper also discusses current challenges at the forefront of genomics-based discrimination, including the selection of detection technology, application of next-generation sequencing, and intratumoral heterogeneity (ITH). In summary, this paper highlights an entrance into the primary stage of molecule-based diagnostics.
Topics: Humans; Lung Neoplasms; Lung; Biomarkers, Tumor; Genomics; High-Throughput Nucleotide Sequencing; Tumor Microenvironment
PubMed: 36958271
DOI: 10.1016/j.ebiom.2023.104508 -
Microbiology Spectrum Dec 2022To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to...
Susceptibilities of Worldwide Isolates of Intrapulmonary Species and Important Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017-2020.
To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to explore antifungal susceptibilities against clinically important isolates of and species (collected from intrapulmonary and sterile body areas, respectively). We applied the CLSI antifungal 2020 and the EUCAST antifungal 2020 guidelines. From 2017 to 2020, isolates of intrapulmonary Aspergillus fumigatus ( = 660), Aspergillus niger ( = 107), Aspergillus flavus ( = 96), Aspergillus terreus ( = 40), and Aspergillus nidulans species complex ( = 26) and sterile site-originated isolates of Candida albicans ( = 1,810), Candida glabrata ( = 894), Candida krusei ( = 120), Candida dubliniensis ( = 107), Candida lusitaniae ( = 82), Candida guilliermondii ( = 28), and Candida auris ( = 7) were enrolled in this study. Using the EUCAST 2020 breakpoints, it was demonstrated that amphotericin B and posaconazole displayed poor susceptibility rates against A. fumigatus isolates (<50% and 18.9%, respectively). In contrast, isavuconazole and itraconazole showed high potency against most isolates (>92%). Most intrapulmonary isolates exhibited MICs of ≤0.06 μg/mL to anidulafungin. Furthermore, intrapulmonary A. fumigatus isolates collected from Italy and the United Kingdom exhibited lower susceptibility to isavuconazole (72.2% and 69%, respectively) than those in the remaining ATLAS participant countries (>85%). Higher isavuconazole MICs against C. auris and C. guilliermondii (1 and 4 μg/mL, respectively) were observed compared to the other five species. Despite the aforementioned MICs and susceptibilities against fungi, research needs to consider the pharmacokinetic (PK) profiles, pharmacodynamic (PD) parameters, and clinical treatment experience with antifungals against specific species. In addition to monitoring the antifungal susceptibilities of clinically important fungi, reviewing the PK/PD indices and the clinical therapy experience of antifungals under evaluation are important to guide an appropriate antifungal prescription. The efficacies of liposomal amphotericin B complex and anidulafungin for the treatment of pulmonary aspergillosis caused by different species need to be periodically evaluated in the future.
Topics: Anidulafungin; Antifungal Agents; Aspergillus; Candida; Drug Resistance, Fungal; Microbial Sensitivity Tests
PubMed: 36314941
DOI: 10.1128/spectrum.02965-22 -
World Journal of Hepatology Nov 2021Hepatopulmonary syndrome (HPS) is characterized by defects in oxygenation caused by intra-pulmonary vasodilation occurring because of chronic liver disease, portal... (Review)
Review
Hepatopulmonary syndrome (HPS) is characterized by defects in oxygenation caused by intra-pulmonary vasodilation occurring because of chronic liver disease, portal hypertension, or congenital portosystemic shunts. Clinical implications of portal hypertension are very well-known, however, awareness of its effect on multiple organs such as the lungs are less known. The presence of HPS in chronic liver disease is associated with increased mortality. Medical therapies available for HPS have not been proven effective and definitive treatment for HPS is mainly liver transplantation (LT). LT improves mortality for patients with HPS drastically. This article provides a review on the definition, clinical presentation, diagnosis, and management of HPS.
PubMed: 34904039
DOI: 10.4254/wjh.v13.i11.1699 -
Journal of Thoracic Disease Sep 2018
PubMed: 30370095
DOI: 10.21037/jtd.2018.08.74 -
Cell Reports Dec 2022The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial...
The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63 progenitors. Here we show that the basal cell transcription factor ΔNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that ΔNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci. Following loss of ΔNp63, intrapulmonary basal progenitors are capable of either airway or alveolar differentiation depending on their surrounding environment both in vitro and in vivo. Uncovering these regulatory mechanisms of dysplastic repair and lung basal cell fate choice highlight potential therapeutic targets to promote functional alveolar regeneration following severe lung injuries.
Topics: Humans; Lung Injury; Alveolar Epithelial Cells; Lung; Cell Differentiation; Influenza, Human; Epithelial Cells
PubMed: 36516758
DOI: 10.1016/j.celrep.2022.111805 -
Clinical Pharmacokinetics Jan 2022A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies... (Review)
Review
A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies comparing plasma and ELF concentrations of antibacterial agents have been published and are summarized in this review. The majority of the studies included in this review determined ELF concentrations of antibacterial agents using bronchoscopy and bronchoalveolar lavage, and this review focuses on intrapulmonary penetration ratios determined with area under the concentration-time curve from healthy human adult studies or pharmacokinetic modeling of various antibacterial agents. If available, pharmacokinetic/pharmacodynamic parameters determined from preclinical murine infection models that evaluated ELF concentrations are also provided. There are also a limited number of recently published investigations of intrapulmonary penetration in critically ill patients with lower respiratory tract infections, where greater variability in ELF concentrations may exist. The significance of these changes may impact the intrapulmonary penetration in the setting of infection, and further studies relating ELF concentrations to clinical response are needed. Phase I drug development programs now include assessment of initial pharmacodynamic target values for pertinent organisms in animal models, followed by evaluation of antibacterial penetration into the human lung to assist in dosage selection for clinical trials in infected patients. The recent focus has been on β-lactam agents, including those in combination with β-lactamase inhibitors, particularly due to the rise of multidrug-resistant infections. This manifests as a large portion of the review focusing on cephalosporins and carbapenems, with or without β-lactamase inhibitors, in both healthy adult subjects and critically ill patients with lower respiratory tract infections. Further studies are warranted in critically ill patients with lower respiratory tract infections to evaluate the relationship between intrapulmonary penetration and clinical and microbiological outcomes. Our clinical research experience with these studies, along with this literature review, has allowed us to outline key steps in developing and evaluating dosage regimens to treat extracellular bacteria in lower respiratory tract infections.
Topics: Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cephalosporins; Humans; Lung; Mice
PubMed: 34651282
DOI: 10.1007/s40262-021-01061-7