Endurance and Resistance Training in Radically Treated Respiratory Cancer patients: A Pilot Study

Introduction. Respiratory cancer and its treatment are known to contribute to muscle weakness and functional impairment. Aim. To assess the effects of rehabilitation in patients with respiratory cancer. Methods. Radically treated respiratory cancer patients were included in a 12-week multidisciplinary rehabilitation program. Results. 16 patients (age: 61 ± 7 years; FEV1: 57 ± 16% pred.) showed a reduced exercise tolerance (VO2max: 56 ± 15% pred.; 6 MWD: 67 ± 11% pred.), muscle force (PImax: 54 ± 22% pred.; QF: 67 ± 16% pred.), and quality of life (CRDQd: 17 ± 5 points; CRDQf: 16 ± 5 points). Exercise tolerance, muscle force, and quality of life improved significantly after rehabilitation. Conclusion. Radically treated patients with respiratory cancer have a decreased exercise capacity, muscle force, and quality of life. 12 weeks of rehabilitation leads to a significant improvement in exercise capacity, respiratory muscle force, and quality of life

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

Prevention of elastase-induced emphysema in placenta growth factor knock-out mice

<p>Abstract</p> <p>Background</p> <p>Although both animal and human studies suggested the association between placenta growth factor (PlGF) and chronic obstructive pulmonary disease (COPD), especially lung emphysema, the role of PlGF in the pathogenesis of emphysema remains to be clarified. This study hypothesizes that blocking PlGF prevents the development of emphysema.</p> <p>Methods</p> <p>Pulmonary emphysema was induced in PlGF knock-out (KO) and wild type (WT) mice by intra-tracheal instillation of porcine pancreatic elastase (PPE). A group of KO mice was then treated with exogenous PlGF and WT mice with neutralizing anti-VEGFR1 antibody. Tumor necrosis factor alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), and VEGF were quantified. Apoptosis measurement and immuno-histochemical staining for VEGF R1 and R2 were performed in emphysematous lung tissues.</p> <p>Results</p> <p>After 4 weeks of PPE instillation, lung airspaces enlarged more significantly in WT than in KO mice. The levels of TNF-α and MMP-9, but not VEGF, increased in the lungs of WT compared with those of KO mice. There was also increased in apoptosis of alveolar septal cells in WT mice. Instillation of exogenous PlGF in KO mice restored the emphysematous changes. The expression of both VEGF R1 and R2 decreased in the emphysematous lungs.</p> <p>Conclusion</p> <p>In this animal model, pulmonary emphysema is prevented by depleting PlGF. When exogenous PlGF is administered to PlGF KO mice, emphysema re-develops, implying that PlGF contributes to the pathogenesis of emphysema.</p

Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.</p> <p>Methods</p> <p>To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.</p> <p>Results</p> <p>Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).</p> <p>Conclusions</p> <p>Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.</p

Is there a uniform approach to the management of diffuse parenchymal lung disease (DPLD) in the UK? A national benchmarking exercise

BACKGROUND: Benchmarking is the comparison of a process to the work or results of others. We conducted a national benchmarking exercise to determine how UK pulmonologists manage common clinical scenarios in diffuse parenchymal lung disease (DPLD), and to determine current use and availability of investigative resources. We compared management decisions to existing international guidelines. METHODS: Consultant members of the British Thoracic Society were mailed a questionnaire seeking their views on the management of three common scenarios in DPLD. They were asked to choose from various management options for each case. Information was also obtained from the respondents on time served as a consultant, type of institution in which they worked and the availability of a local radiologist and histopathologist with an interest/expertise in thoracic medicine. RESULTS: 370 out of 689 consultants replied (54% response rate). There were many differences in the approach to the management of all three cases. Given a scenario of relapsing pulmonary sarcoidosis in a lady with multiple co-morbidities, half of respondents would institute treatment with a variety of immunosuppressants while a half would simply observe. 42% would refer a 57-year old lady with new onset DPLD for a surgical lung biopsy, while a similar number would not. 80% would have referred her for transplantation, but a fifth would not. 50% of consultants from district general hospitals would have opted for a surgical biopsy compared to 24% from cardiothoracic centres: this may reflect greater availability of a radiologist with special interest in thoracic imaging in cardiothoracic centres, obviating the need for tissue diagnosis. Faced with an elderly male with high resolution CT thorax (HRCT) evidence of usual interstitial pneumonia (UIP), three quarters would observe, while a quarter would start immunosuppressants. 11% would refer for a surgical biopsy. 14% of UK pulmonologists responding to the survey revealed they had no access to a radiologist with an interest in thoracic radiology. CONCLUSION: From our survey, it appears there is a lack of consensus in the management of DPLD. This may reflect lack of evidence, lack of resources or a failure to implement current guidelines

Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

BACKGROUND: An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.</p

Angiogenesis in Interstitial Lung Diseases: a pathogenetic hallmark or a bystander?

The past ten years parallels have been drawn between the biology of cancer and pulmonary fibrosis. The unremitting recruitment and maintenance of the altered fibroblast phenotype with generation and proliferation of immortal myofibroblasts is reminiscent with the transformation of cancer cells. A hallmark of tumorigenesis is the production of new blood vessels to facilitate tumor growth and mediate organ-specific metastases. On the other hand several chronic fibroproliferative disorders including fibrotic lung diseases are associated with aberrant angiogenesis. Angiogenesis, the process of new blood vessel formation is under strict regulation determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively. While numerous studies have examined so far the interplay between aberrant vascular and matrix remodeling the relative role of angiogenesis in the initiation and/or progression of the fibrotic cascade still remains elusive and controversial. The current article reviews data concerning the pathogenetic role of angiogenesis in the most prevalent and studied members of ILD disease-group such as IIPs and sarcoidosis, presents some of the future perspectives and formulates questions for potential further research