An optimized method for IgE-mediated degranulation of human lung mast cells.

Background: Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma.

Uniportal video-assisted thoracic surgery: segmentectomy versus lobectomy-early outcomes.

Objectives: To assess the feasibility and safety of uniportal video-assisted thoracoscopic pulmonary segmentectomy compared with lobectomy by studying early postoperative outcomes.

Methods: We included all patients who underwent uniportal segmentectomy and lobectomy between 2017 and 2022 at Karolinska University Hospital. Early clinical outcomes were compared between the uniportal segmentectomy and lobectomy groups.

Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8 T cells towards the center of human lung tumors.

Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little is known about the spatial distribution of tissue-resident lymphocyte subsets in lung tumors. Using high-parameter flow cytometry, we identified an accumulation of tissue-resident lymphocytes including tissue-resident NK (trNK) cells and CD8 tissue-resident memory T (T) cells toward the center of human non-small cell lung carcinomas (NSCLC).

Defining the contractile prostanoid component in hyperosmolar-induced bronchoconstriction in human small airways.

Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the contractile prostanoid component of EIB, using an ex vivo model where intact segments of bronchi (inner diameter 0.5-2 mm) isolated from human lung tissue and subjected to mannitol.

Analysis of human lung mast cells by single cell RNA sequencing.

Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MC and MC, where MC express the mast cell protease tryptase and MC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G.

Cysteinyl-maresin 3 inhibits IL-13 induced airway hyperresponsiveness through alternative activation of the CysLT receptor.

Background: Cysteinyl-maresins, also known as maresin-conjugates in tissue regeneration (MCTRs), are recently discovered lipid mediators proposed to reduce airway inflammation.

Objective: To investigate the influence of MCTRs on IL-13-induced airway hyperresponsiveness in isolated human and mice airways.

Methods: Before responsiveness to contractile agonists were assessed in myographs, human small bronchi were cultured for 2 days and mouse tracheas were cultured for 1-4 days.

Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.

Background: Activation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease-related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fibre contractile function and assess skeletal muscle SMase activity in heart failure patients.

Methods: The effects of SMase on force production and intracellular Ca handling were investigated in single intact human muscle fibres.

Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity.

Background: Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.

Methods: Human lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen™ kit.

Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood.

Human adaptive-like "memory" CD56CD16 natural killer (NK) cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated in recent years and are currently explored as a treatment strategy for hematological cancers. However, treatment of solid tumors remains limited due to insufficient NK cell tumor infiltration, and it is unknown whether large expansions of adaptive-like NK cells that are equipped for tissue residency and tumor homing exist in peripheral tissues. Here, we show that human lung and blood contains adaptive-like CD56CD16 NK cells with hallmarks of tissue residency, including expression of CD49a.

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing.

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127 ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs.

Erratum to video-assisted thoracoscopic versus open thoracotomy lobectomy: a Swedish nationwide cohort study.

[This corrects the article DOI: 10.21037/jtd.2018.

Uniportal versus multiportal video-assisted thoracic surgery for lung cancer.

Background: Video-assisted thoracic surgery (VATS) lobectomy is the recommended surgical approach for patients with stage I lung cancer. Whether a multiportal or a uniportal approach is preferable remains unclear. The aim of this study was to evaluate the safety of implementing uniportal VATS lobectomy into the treatment program of lung cancer patients.

IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways.

Background: Specific inflammatory pathways are indicated to contribute to severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.

Objective: This experimental study in human small bronchi aimed to provide insight into which of the type 2 and type 17 cytokines cause hyperresponsiveness of airway smooth muscle.

Methods: Explanted small bronchi isolated from human lung tissue and human airway smooth muscle cells were treated for 2 and 1 day(s), respectively, with 100 ng/mL of IL-4, IL-5, IL-13, or IL-17A, and contractile responses, Ca mobilization, and receptor expression were assessed.

Impaired sarcoplasmic reticulum Ca release is the major cause of fatigue-induced force loss in intact single fibres from human intercostal muscle.

Key Points: Changes in intramuscular Ca handling contribute to development of fatigue and disease-related loss of muscle mass and function. To date, no data on human intact living muscle fibres have been described. We manually dissected intact single fibres from human intercostal muscle and simultaneously measured force and myoplasmic free [Ca ] at physiological temperature.

Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells.

Human lung tissue-resident NK cells (trNK cells) are likely to play an important role in host responses towards viral infections, inflammatory conditions and cancer. However, detailed insights into these cells are still largely lacking. Here we show, using RNA sequencing and flow cytometry-based analyses, that subsets of human lung CD69CD16 NK cells display hallmarks of tissue-residency, including high expression of CD49a, CD103, and ZNF683, and reduced expression of SELL, S1PR5, and KLF2/3.

Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection.

Background: Clinical research supports that exercise-induced bronchoconstriction (EIB) is caused by hyperosmolar triggering of mast cells. The reaction can be mimicked by inhalation of mannitol, but it has paradoxically previously not been possible to replicate this mode of action of mannitol in isolated airways.

Objective: We sought to establish an ex vivo model of EIB in human small bronchi.

Influenza A Virus Infection Induces Hyperresponsiveness in Human Lung Tissue-Resident and Peripheral Blood NK Cells.

NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, the detailed functional capacity of human lung and peripheral blood NK cells remains to be determined in IAV and other respiratory viral infections. Here, we investigated the effects of IAV infection on human lung and peripheral blood NK cells and following clinical infection.

An Optimized Protocol for the Isolation and Functional Analysis of Human Lung Mast Cells.

Mast cells are tissue-resident inflammatory cells defined by their high granularity and surface expression of the high-affinity IgE receptor, FcεRI, and CD117/KIT, the receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically and functionally. Human mast cells are generally divided into two main subtypes based on their protease content; the mucosa-associated MC (tryptase positive and chymase negative mast cell) and the connective tissue associated-residing MC (tryptase and chymase positive mast cell).

Video-assisted thoracoscopic versus open thoracotomy lobectomy: a Swedish nationwide cohort study.

Background: The aim of this nationwide observational cohort study was to investigate the early postoperative complications and long-term survival following video-assisted thoracoscopic surgery (VATS) lobectomy compared to open thoracotomy lobectomy for early stage non-small cell lung cancer (NSCLC).

Methods: We used the Swedish national quality register for general thoracic surgery and included all patients who underwent lobectomy for NSCLC during 2012-2015. We compared postoperative complications and long-term survival in patients who underwent VATS lobectomy at our institution to patients who underwent open lobectomy at the other seven hospitals in Sweden.

Surgery for pulmonary metastases from colorectal cancer: survival and prognostic factors.

Background: This study aimed to describe overall survival following pulmonary metastasectomy for colorectal cancer (CRC) in Sweden, and to assess the discrimination of a recently proposed risk prediction model.

Methods: Individual-level data of 756 patients who underwent resection of pulmonary metastases from CRC between 2009 and 2015 were obtained from ThoR, a Swedish national quality register for thoracic surgery. We classified patients into three risk categories according to the number of preoperative risk factors [age, disease-free interval (DFI), presence of extrathoracic lesions, number of pulmonary metastases] established in a prior study.

Long-term survival after surgery for pulmonary metastases from colorectal cancer: an observational cohort study.

Background: Evidence for pulmonary metastasectomy following colorectal cancer (CRC) is scarce. The aim of the study was to investigate long-term survival and identify prognostic factors to aid patient selection.

Methods: We included all patients who underwent pulmonary resections for CRC metastases between January 01, 2004 and December 31, 2015 in a population-based cohort study.

Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69CD56 cells.

Background: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer.

Objective: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level.

Self-Reported Physical Quality of Life Before Thoracic Operations Is Associated With Long-Term Survival.

Background: The aim was to analyze the association between baseline self-reported health-related quality of life and long-term survival after thoracic operations.

Methods: In a prospective population-based cohort study, we included patients scheduled for thoracic operations and obtained information about preoperative health-related quality of life using the validated quality-of-life instrument Short Form-36. Patients were categorized according to higher or lower physical and mental component scores, compared with an age- and sex-matched reference population.