scholarly journals Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study

Author(s):  
Benedikt Kowalski ◽  
Alan Valaperti ◽  
Pascal Bezel ◽  
Urs C. Steiner ◽  
Dieter Scholtze ◽  
...  

Abstract Purpose Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been fully understood. The aim of this cross-sectional case–control study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICIaP compared to controls consisting of healthy individuals, patients with lung cancer and patients with interstitial lung diseases (ILD) other than ICIaP. Methods From January 2018 until June 2019, 401 adult patients with various lung diseases were prospectively enrolled in a BALF- and serum biobank, called BALOTHEK. Of these, 12 patients were diagnosed with ICIaP (Pembrolizumab, Ipilimumab, or both, and Durvalumab) serving as case group. Subjects with one of three diagnosis groups from BALOTHEK, including lung cancer, ILD other than ICIaP, and healthy individuals, served as matched controls. The following 11 cytokines were simultaneously analyzed in BALF and serum of each study participant: interferon gamma, tumor necrosis factor alpha, interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13 and IL-17A. This study was approved by the local ethic review committee (BASEC-ID 2017-02,307 and 2018-01,724). Results Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control groups. For the investigated cytokines in BALF, a significant increase of IL-6 level was shown for patients with ICIaP compared to control groups (p = 0.031, adjusted for multiple comparisons). Conclusion Cytokine profile assessed in BALF shows promising potential for facilitating diagnosis and understanding of pathophysiology of ICIaP. IL-6 may not only contribute to better understanding of pathophysiology but also herald therapeutic implications for Tocilizumab.

Respirology ◽  
2015 ◽  
Vol 20 (8) ◽  
pp. 1248-1254 ◽  
Author(s):  
Evgenia C. Panagiotopoulou ◽  
Sotirios Fouzas ◽  
Konstantinos Douros ◽  
Irene-Eva Triantaphyllidou ◽  
Christina Malavaki ◽  
...  

2017 ◽  
Vol 18 (3) ◽  
pp. 616 ◽  
Author(s):  
Paulo Souza-Fonseca-Guimaraes ◽  
Fernando Guimaraes ◽  
Caroline Natânia De Souza-Araujo ◽  
Lidiane Maria Boldrini Leite ◽  
Alexandra Cristina Senegaglia ◽  
...  

Author(s):  
Pascal Bezel ◽  
Alan Valaperti ◽  
Urs Steiner ◽  
Dieter Scholtze ◽  
Stephan Wieser ◽  
...  

Abstract Introduction Lung cancer is the leading cause of death by cancer. In recent years, immunotherapy with checkpoint inhibitors (ICI) emerged as a promising new therapeutic approach. However, a deeper understanding of the immunologic responses adjacent to the tumor known as tumor microenvironment (TME) is needed. Our study investigated TME of lung cancer by analyzing cytokines in bronchoalveolar lavage fluid (BALF). Materials and methods Between January 2018 and June 2019, 119 patients were prospectively enrolled in this study. For each cancer patient, levels of 16 cytokines (fractalkine, granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukins (IL): IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, and IL-23) were measured in BALF and serum and compared to healthy individuals and patients with other lung diseases. Results There were several significant differences of cytokine levels of patients with lung cancer compared to healthy individuals. However, none of them remained in the multivariate analysis compared to other lung diseases in either BALF or serum. Furthermore, there were no significant differences between the groups in cell differentiation of either BALF or serum. Cytokine levels in BALF were generally near the lower detection limit and showed almost no correlation with their respective levels measured in serum of the same individual. Conclusions Cytokines in BALF and serum of lung cancer patients may indicate unspecific inflammation. BAL is not recommendable as a tool to investigate TME of lung cancer. Therefore, cytokines measured in BALF are probably not appropriate as predictors in patients treated with ICIs.


Healthcare ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 320
Author(s):  
Fayaz Khan ◽  
Mohamed Faisal Chevidikunnan

Stroke is a major cause of disability worldwide, and balance impairments are common disabling factors in patients with stroke, leading to falls. Thus, the study objectives were as follows: (i) To find the prevalence of balance impairment among patients with stroke. (ii) To find out the factors associated with balance impairment in patients with stroke. This cross-sectional retrospective case control study involved eighty-one post stroke patients with a mean age of 58.36 ± 14.06, recruited from six hospitals, who underwent an assessment of balance, walking speed, depression and isometric strength of the ankle and knee. These patients were later categorized into subjects with good balance (<45) in the Berg balance scale (BBS) and those with poor balance (≥45), as cases and controls, to assess the factors associated with balance impairment using binary logistic regression. The prevalence of balance impairment among patients with stroke was 48.1%. The reduction in power of knee flexors (OR = 0.858), knee extensors (OR = 0.880) and ankle dorsiflexors (OR = 0.820) was found to be significantly associated with balance impairment, along with speed (OR = 1.187 (95% CI = 1.100, 1.280)), depression (OR = 1.331 (95% CI = 1.055–1.679)) and activities of daily living (OR = 0.313 (95% CI = 0.150–0.650)). In summary, around half of the patients with stroke exhibited balance impairments, with females being more prone.


2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi72-vi73
Author(s):  
Daniel Lachance ◽  
Harsheen Kaur ◽  
Conor Ryan ◽  
Youn Ho Sheen ◽  
Hee Yun Seol ◽  
...  

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