Browsing by Subject "lung"

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  • Rossi, Heini; Virtala, Anna-Maija Kristiina; Raekallio, Marja Riitta; Rahkonen, Emmi; Rajamäki, Minna; Mykkänen, Anna Kristina (2018)
    Most equine lower respiratory diseases present as increased airway neutrophilia, which can be detected in tracheal wash (TW) or bronchoalveolar lavage fluid (BALE) cytology samples. The aim was to compare the TW and BALF results in a population of client-owned horses with and without clinical respiratory disease signs. A secondary aim was to determine the sensitivity (Se) and specificity (Sp) of TW and BALF neutrophilia in detecting respiratory disease. The cutoff values for neutrophils were also evaluated. Retrospective data from 154 horses of various breeds that had been subject to both TW and bronchoalveolar lavage (BAL) sampling at rest during 2009-2015 were used. The horses were divided into three groups based on the presenting signs, physical examination, and endoscopy mucus score. Neutrophil counts of >20% in TW and >5% in BAL were considered abnormal. Cytology results between groups, correlations between 1W and BALF cell types, and tracheal mucus score were analyzed. Two graph receiving operating characteristic (ROC) curves of the neutrophil percentage values of TW and BALF were created to determine the optimal cutoff values and to calculate the diagnostic Se and Sp for diagnosing airway inflammation in horses with and without clinical respiratory signs. The Se and Sp of TW and BALF neutrophil percentages were further estimated using a two-test one-population Bayesian latent class model. The two tests showed substantial agreement, and only 17.5% of the horses were classified differently (healthy vs. diseased). The neutrophil percentage was found to correlate between TW and BALF. The Se and Sp of TW were generally higher than for BAL when estimated with area under the curve or Bayesian model. Cutoff values of 17.7% for TW and 7% for BALF were indicated by the ROCs. We conclude that TW is a more sensitive and specific method in our patient population. We suggest that the current neutrophil cutoff values of 20% for 1W and 5% for BALE would still be appropriate to use in clinical diagnosis of airway inflammation. However, further studies with other cell types and in other populations are warranted to determine the best sampling method for individual horses.
  • Brownlie, Demi; Scharenberg, Marlena; Mold, Jeff E.; Hard, Joanna; Kekäläinen, Eliisa; Buggert, Marcus; Nguyen, Son; Wilson, Jennifer N.; Al-Ameri, Mamdoh; Ljunggren, Hans-Gustaf; Marquardt, Nicole; Michaelsson, Jakob (2021)
    Human adaptive-like "memory" CD56(dim)CD16(+) 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 CD56(bright)CD16(-) NK cells with hallmarks of tissue residency, including expression of CD49a. Expansions of adaptive-like lung tissue-resident NK (trNK) cells were found to be present independently of adaptive-like CD56(dim)CD16(+) NK cells and to be hyperresponsive toward target cells. Together, our data demonstrate that phenotypically, functionally, and developmentally distinct subsets of adaptive-like NK cells exist in human lung and blood. Given their tissue-related character and hyperresponsiveness, human lung adaptive-like trNK cells might represent a suitable alternative for therapies targeting solid tumors.
  • Scharenberg, Marlena; Vangeti, Sindhu; Kekäläinen, Eliisa; Bergman, Per; Al-Ameri, Mamdoh; Johansson, Niclas; Sonden, Klara; Falck-Jones, Sara; Färnert, Anna; Ljunggren, Hans-Gustaf; Michaelsson, Jakob; Smed-Sörensen, Anna; Marquardt, Nicole (2019)
    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 in vitro and ex vivo following clinical infection. IAV infection of lung- and peripheral blood-derived mononuclear cells in vitro induced NK cell hyperresponsiveness to K562 target cells, including increased degranulation and cytokine production particularly in the CD56(bright)CD16(-) subset of NK cells. Furthermore, lung CD16(-) NK cells showed increased IAV-mediated but target cell-independent activation compared to CD16(+) lung NK cells or total NK cells in peripheral blood. IAV infection rendered peripheral blood NK cells responsive toward the normally NK cell-resistant lung epithelial cell line A549, indicating that NK cell activation during IAV infection could contribute to killing of surrounding non-infected epithelial cells. In vivo, peripheral blood CD56(dim)CD16(+) and CD56(bright)CD16(-) NK cells were primed during acute IAV infection, and a small subset of CD16(-) CD49a(+)CXCR3(+) NK cells could be identified, with CD49a and CXCR3 potentially promoting homing to and tissue-retention in the lung during acute infection. Together, we show that IAV respiratory viral infections prime otherwise hyporesponsive lung NK cells, indicating that both CD16(+) and CD16(-) NK cells including CD16(-)CD49a(+) tissue-resident NK cells could contribute to host immunity but possibly also tissue damage in clinical IAV infection.
  • Määttä, Merita; Laurila, Henna P.; Holopainen, Saila; Aaltonen, Kaisa; Lilja-Maula, Liisa; Viitanen, Sanna; Rajamaki, Minna M. (2021)
    Background Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, interstitial lung disease that mainly affects West Highland white terriers (WHWTs) and is characterized by excessive deposition of extracellular matrix (ECM) in the lung. Matrix metalloproteinases (MMPs) participate in remodeling of ECM. Objectives To compare metalloproteinase-2, -7 and -9 activities in blood or bronchoalveolar lavage fluid (BALF) samples or both of CIPF WHWTs with healthy WHWTs, healthy dogs of other breeds, and dogs with other lung diseases and determine if these MMPs could be used as diagnostic and prognostic markers for CIPF. Animals Forty-four CIPF WHWTs, 24 dogs with chronic bronchitis (CB), 17 with eosinophilic bronchopneumopathy (EBP), 10 with bacterial pneumonia, 39 healthy WHWTs, and 35 healthy dogs of other breeds. Methods Cross-sectional observational study. Pro-MMP and active MMP activities were analyzed by zymography. Results In serum, significantly higher (P <.01) pro-MMP-7 activities were observed in CIPF WHWTs compared to healthy dogs of other breeds, dogs with CB and dogs with EBP. In BALF of CIPF WHWTs, both pro-MMP-9 and pro-MMP-2 activities were significantly higher (P <.01) compared to healthy WHWTs, but these differences were not detected in plasma. The CIPF WHWTs had significantly higher (P <.05) activities of pro-MMP-9 compared to dogs with CB and of pro-MMP-2 compared to dogs with CB and EBP. No statistically significant prognostic factors were observed in CIPF WHWTs. Conclusions and clinical relevance Serum MMP-7 and BALF MMP-2 and -9 potentially may be useful diagnostic markers but not prognostic markers for CIPF.
  • Kainu, Annette; Timonen, Kirsi L.; Vanninen, Esko; Sovijarvi, Anssi R. (2018)
    Inspiratory spirometry is used in evaluation of upper airway disorders e.g. fixed or variable obstruction. There are, however, very few published data on normal values for inspiratory spirometry. The main aim of this study was to produce reference values for inspiratory spirometry for healthy Finnish adults.Inspiratory spirometry was preplanned to a sample of the Finnish spirometry reference values sample. Data was successfully retrieved from 368 healthy nonsmoking adults (132 males) between 19 and 83years of age. Reference equations were produced for forced inspiratory vital capacity (FIVC), forced inspiratory volume in one second (FIV1), FIV1/FIVC, peak inspiratory flow (PIF) and the ratios of FIV1/forced expiratory volume in one second and PIF/peak expiratory flow. The present values were compared to PIF values from previously used Finnish study of Viljanen etal. (1982) reference values and Norwegian values for FIV1, FIVC and FIV1/FIVC presented by Gulsvik etal. (2001). The predicted values from the Gulsvik etal. (2001), provided a good fit for FIVC, but smaller values for FIV1 with mean 108.3 and 109.1% of predicted values for males and females, respectively. PIF values were 87.4 and 91.2% of Viljanen etal. (1982) predicted values in males and females, respectively. Differences in measurement methods and selection of results may contribute to the observed differences. Inspiratory spirometry is technically more demanding and needs repeatability criteria to improve validity. New reference values are suggested to clinical use in Finland when assessing inspiratory spirometry. Utility of inspiratory to expiratory values indices in assessment of airway collapse need further study.
  • Auråen, Henrik; Schultz, Hans Henrik L.; Hämmäinen, Pekka; Riise, Gerdt C.; Larsson, Hillevi; Hansson, Lennart; Dellgren, Göran; Perch, Michael; Geiran, Odd; Fiane, Arnt E.; Iversen, Martin; Holm, Are Martin (2018)
    BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.