Lung Compliance and Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases, with resulting pathological and pathophysiological changes in the lung. The main pathophysiological aspects of the disease are airflow obstruction and hyperinflation. The mechanical properties of the respiratory system and its component parts are studied by determining the corresponding volume-pressure (P-V) relationships. The consequences of the inflammatory response on the lung structure and function are depicted on the volume-pressure relationships

Tiotropium bromide exerts anti-inflammatory effects during resistive breathing, an experimental model of severe airway obstruction

Introduction: Resistive breathing (RB), a hallmark of obstructive airway diseases, is characterized by strenuous contractions of the inspiratory muscles that impose increased mechanical stress on the lung. RB is shown to induce pulmonary inflammation in previous healthy animals. Tiotropium bromide, an anticholinergic bronchodilator, is also shown to exert anti-inflammatory effects. The effect of tiotropium on RB-induced pulmonary inflammation is unknown. Methods: Adult rats were anesthetized, tracheostomized and breathed spontaneously through a two-way non-rebreathing valve. Resistances were connected to the inspiratory and/or expiratory port, to produce inspiratory resistive breathing (IRB) of 40% or 50% Pi/Pi,max (40% and 50% IRB), expiratory resistive breathing (ERB) of 60% Pe/Pe,max (60% ERB) or combined resistive breathing (CRB) of both 40% Pi/Pi,max and 60% Pe/Pe,max (40%/60% CRB). Tiotropium aerosol was inhaled prior to RB. After 6 h of RB, mechanical parameters of the respiratory system were measured and bronchoalveolar lavage (BAL) was performed. IL-1β and IL-6 protein levels were measured in lung tissue. Lung injury was estimated histologically. Results: In all, 40% and 50% IRB increased macrophage and neutrophil counts in BAL and raised IL-1β and IL-6 lung levels, tissue elasticity, BAL total protein levels and lung injury score. Tiotropium attenuated BAL neutrophil number, IL-1β, IL-6 levels and lung injury score increase at both 40% and 50% IRB. The increase in macrophage count and protein in BAL was only reversed at 40% IRB, while tissue elasticity was not affected. In all, 60% ERB raised BAL neutrophil count and total protein and reduced macrophage count. IL-1β and IL-6 levels and lung injury score were increased. Tiotropium attenuated these alterations, except for the decrease in macrophage count and the increase in total protein level. In all, 40%/60% CRB increased macrophage and neutrophil count in BAL, IL-1β and IL-6 levels, tissue elasticity, total protein in BAL and histological injury score. Tiotropium attenuated the aforementioned alterations. Conclusion: Tiotropium inhalation attenuates RB-induced pulmonary inflammation. © 2017 Toumpanakis et al

Tiotropium bromide exerts anti-inflammatory effects during resistive breathing, an experimental model of severe airway obstruction

Dimitrios Toumpanakis,1,2 Konstantinos Loverdos,1,2 Vassiliki Tzouda,1,2 Vyronia Vassilakopoulou,1,2 Eleni Litsiou,1,2 Christina Magkou,3 Vassiliki Karavana,1,2 Michael Pieper,4 Theodoros Vassilakopoulos1,2 1First Critical Care Department, Pulmonary Unit, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital, 2George P. Livanos and Marianthi Simou Laboratories, Thorax Foundation, 3Department of Pathology, Evangelismos General Hospital, Athens, Greece; 4Boehringer Ingelheim Pharma GmbH & Co. KG Div. Research Germany, Biberach, Germany Introduction: Resistive breathing (RB), a hallmark of obstructive airway diseases, is characterized by strenuous contractions of the inspiratory muscles that impose increased mechanical stress on the lung. RB is shown to induce pulmonary inflammation in previous healthy animals. Tiotropium bromide, an anticholinergic bronchodilator, is also shown to exert anti-inflammatory effects. The effect of tiotropium on RB-induced pulmonary inflammation is unknown.Methods: Adult rats were anesthetized, tracheostomized and breathed spontaneously through a two-way non-rebreathing valve. Resistances were connected to the inspiratory and/or expiratory port, to produce inspiratory resistive breathing (IRB) of 40% or 50% Pi/Pi,max (40% and 50% IRB), expiratory resistive breathing (ERB) of 60% Pe/Pe,max (60% ERB) or combined resistive breathing (CRB) of both 40% Pi/Pi,max and 60% Pe/Pe,max (40%/60% CRB). Tiotropium aerosol was inhaled prior to RB. After 6 h of RB, mechanical parameters of the respiratory system were measured and bronchoalveolar lavage (BAL) was performed. IL-1β and IL-6 protein levels were measured in lung tissue. Lung injury was estimated histologically.Results: In all, 40% and 50% IRB increased macrophage and neutrophil counts in BAL and raised IL-1β and IL-6 lung levels, tissue elasticity, BAL total protein levels and lung injury score. Tiotropium attenuated BAL neutrophil number, IL-1β, IL-6 levels and lung injury score increase at both 40% and 50% IRB. The increase in macrophage count and protein in BAL was only reversed at 40% IRB, while tissue elasticity was not affected. In all, 60% ERB raised BAL neutrophil count and total protein and reduced macrophage count. IL-1β and IL-6 levels and lung injury score were increased. Tiotropium attenuated these alterations, except for the decrease in macrophage count and the increase in total protein level. In all, 40%/60% CRB increased macrophage and neutrophil count in BAL, IL-1β and IL-6 levels, tissue elasticity, total protein in BAL and histological injury score. Tiotropium attenuated the aforementioned alterations.Conclusion: Tiotropium inhalation attenuates RB-induced pulmonary inflammation. Keywords: resistive breathing, inflammation, tiotropium bromid

Dose- and time-dependent effects of lipopolysaccharide on technetium-99-m-labeled diethylene-triamine pentaacetatic acid clearance, respiratory system mechanics and pulmonary inflammation

Intratracheal administration of lipopolysaccharide (LPS) in animals is a commonly used model of acute lung injury, characterized by increased alveolar-capillary membrane permeability causing protein-rich edema, inflammation, deterioration of lung mechanical function and impaired gas exchange. Technetium-99-m-labeled diethylene-triamine pentaacetatic acid (99mTc-DTPA) scintigraphy is a non-invasive technique to assess lung epithelial permeability. We hypothesize that the longer the exposure and the higher the dose of LPS the greater the derangement of the various indices of lung injury. After 3, 6 and 24 h of 5 or 40 mg LPS intratracheally administration, 99mTc-DTPA was instilled in the lung. Images were acquired for 90 min with a g-camera and the radiotracer clearance was estimated. In another subgroup, the mechanical properties of the respiratory system were estimated with the forced oscillation technique and static pressure-volume curves, 4.5, 7.5 and 25.5 h post-LPS (iso-times with the end of 99mTc-DTPA scintigraphy). Bronchoalveolar lavage (BAL) was performed and a lung injury score was estimated by histology. Lung myeloperoxidase (MPO) activity was measured. 99mTc-DTPA clearance increased in all LPS challenged groups compared with control. DTPA clearance presented a U-shape time course at the lower dose, while LPS had a declining effect over time at the larger dose. At 7.5 and 25.5 h post-LPS, tissue elasticity was increased and static compliance decreased at both doses. Total protein in the BAL fluid increased at both doses only at 4.5 h Total lung injury score and MPO activity were elevated in all LPS-treated groups. There is differential time- and dose-dependency of the various indices of lung injury after intratracheally LPS instillation in rats. © 2013 by the Society for Experimental Biology and Medicine

Real-World Data on Health-Related Quality of Life Assessment in Patients With Breast Cancer Receiving Subcutaneous Trastuzumab

Purpose: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (anti-HER2) antibody delivered intravenously, has revolutionized the treatment of patients with breast cancer overexpressing HER2 protein. Recently, a newer subcutaneous formulation was shown to have comparable efficacy to the initial intravenous trastuzumab. In this study, we aimed to evaluate the impact of subcutaneous trastuzumab on the health-related quality of life (HRQoL) of patients diagnosed with early or metastatic HER2-overexpressing breast cancer. Methods: Patients were provided with the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and the BR-23 questionnaires. The scoring of questionnaires and patient’s sociodemographic and clinicopathologic characteristics were recorded and analyzed by descriptive and correlation statistics employing t test and 2-way analysis of variance. Results: A total of 163 patients agreed to participate in the study. About 90 of 163 patients (55.21%) received subcutaneous trastuzumab and 21 patients intravenous trastuzumab (12.88%). A control group of 52 HER2+ patients received chemotherapy without trastuzumab (31.90%). Patients receiving subcutaneous trastuzumab were older and of more advanced disease stage compared with those receiving chemotherapy (58.5 vs 51 years, 39.8% vs 28.8% advanced disease). In univariate analysis, subcutaneous trastuzumab was associated with less nausea and vomiting (P =.002) but worse cognitive function (P =.013) and dyspnea (P =.042). Patients who have received >8 cycles of subcutaneous trastuzumab reported less diarrhea (P =.049) and systemic therapy side effects (P =.015). Multivariate analysis showed that patients without comorbidity receiving subcutaneous trastuzumab had less treatment side effects, less upset by hair loss, and higher emotional functioning. Of note, mastectomy and subcutaneous trastuzumab were associated with improved role functioning (P =.021). In metastatic disease, no negative impact of subcutaneous trastuzumab on HRQoL was found. Conclusions: The administration of subcutaneous trastuzumab improved certain symptoms and did not adversely affect most of the assessed functional scales. Particularly, in the metastatic setting, subcutaneous trastuzumab had no negative impact on HRQoL. © The Author(s) 2018

Carcinoembryonic antigen and carbohydrate antigen 19-9 serum levels in non-small cell lung cancer

Purpose: Τo investigate the potential diagnostic and prognostic role of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) serum levels in non-small cell lung cancer (NSCLC). Methods: One hundred consecutive patients with newly diagnosed primary NSCLC were included in this study (88 men and 12 women). Blood was drawn before any kind of treatment and the collected serum was processed using chemiluminescence in order CEA and CA 19-9 levels to be measured. Results: No significant associations between CEA or CA 19-9 levels and any tested clinical and pathological parameter were detected. Moreover, CEA levels did not seem to affect survival. On the other hand, patients with high CA 19-9 values (≥37 IU/ml) (median survival: 8 months) had a shorter overall survival than patients with low CA 19-9 values (<37 IU/ml) (median survival: 13 months) (p=0.026). However, CA 19-9 levels did not remain an independent prognostic factor in the multivariate survival analysis (p=0.114). Conclusion: CEA and CA 19-9 serum levels do not seem to have any diagnostic role in NSCLC. With regard to their prognostic role, CEA values do not seem to affect the prognosis in NSCLC. However, high CA 19-9 values are associated with worse prognosis. © 2017 Zerbinis Publications. All rights reserved