197 results on '"Rabinovich, Roberto"'
Search Results
152. Validity of Six Activity Monitors in Chronic Obstructive Pulmonary Disease: A Comparison with Indirect Calorimetry.
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Remoortel, Hans Van, Raste, Yogini, Louvaris, Zafeiris, Giavedoni, Santiago, Burtin, Chris, Langer, Daniel, Wilson, Frederick, Rabinovich, Roberto, Vogiatzis, Ioannis, Hopkinson, Nicholas S., and Troosters, Thierry
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OBSTRUCTIVE lung diseases ,METABOLISM ,CALORIMETRY ,ACTIGRAPHY ,RESPIRATORY obstructions ,PHYSICAL fitness - Abstract
Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD). Various activity monitors are available but their validity is poorly established. The aim was to evaluate the validity of six monitors in patients with COPD. We hypothesized triaxial monitors to be more valid compared to uniaxial monitors. Thirty-nine patients (age 68±7years, FEV
1 54±18%predicted) performed a one-hour standardized activity protocol. Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile). Validity was evaluated by correlation analysis between indirect calorimetry (VO2 ) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking. Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73). Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45). The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds. The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities. The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. [ABSTRACT FROM AUTHOR]- Published
- 2012
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153. Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population.
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Haq, Imran, Chappell, Sally, Johnson, Simon R, Lotya, Juzer, Daly, Leslie, Morgan, Kevin, Guetta-Baranes, Tamar, Roca, Josep, Rabinovich, Roberto, Millar, Ann B, Donnelly, Seamas C, Keatings, Vera, MacNee, William, Stolk, Jan, Hiemstra, Pieter S, Miniati, Massimo, Monti, Simonetta, O'Connor, Clare M, and Kalsheker, Noor
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OBSTRUCTIVE lung diseases ,GENETIC polymorphisms ,METALLOPROTEINASES ,NUCLEOTIDE sequence - Abstract
Background: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. Methods: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Results: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Conclusions: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV
1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity. [ABSTRACT FROM AUTHOR]- Published
- 2010
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154. Identification of Human Immunodeficiency Virus Type 1 Subtypes B and F, B/F Recombinant and Dual Infection with these Subtypes in Argentina.
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Fernández-Medina, Daniela, Jansson, Marianne, Rabinovich, Roberto D., Libonatti, Osvaldo, and Wigzell, Hans
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HIV ,HIV-positive persons - Abstract
DNA sequences encoding the third variable region (V3) of human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120 were obtained from 18 infected individuals residing in different regions of Argentina. Proviral DNA representing the env V3 region was obtained by PCR from uncultured peripheral blood mononuclear cells (PBMC) and genetic heterogeneity was examined by phylogenetic analysis. Sequences representing the gag p17 region were also obtained for a subset of these samples. Moreover, 1 sample that it was not possible to classify according to initial phylogenetic analysis was further analysed by molecular cloning of both V3 and p17 regions. Phylogenetic analysis according to different methodologies were performed comparing obtained sequences with a set of reference sequences representing previously characterized HIV-1 subtypes. The recombinant identification program (RIP) was used to study the presence of possible recombinant sequences. Phylogenetic analysis demonstrated that viruses representing both subtypes B and F are circulating among HIV-1 infected individuals in Argentina. In addition, RIP analysis showed that an initially unclassified sequence exhibited similarities to subtypes B and F in different fragments of the V3 region. Separate phylogenetic analysis of each of these fragments revealed divergent clustering, suggesting that this sequence harbours a point of recombination within the V3 loop. Interestingly, we also identified a dually infected individual with viruses belonging to subtypes B and F, as demonstrated by molecular cloning analysis of the env V3 and the gag p17 regions. Taken together, our study shows that both subtypes B and F are circulating in different regions of Argentina. Moreover, the data presented here show that dual infections with subtypes B and F can occur, and consequently B/F recombinant sequences are arising in the region. [ABSTRACT FROM AUTHOR]
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- 1999
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155. Modification of Junin Virus Neurotropism in Mice by Selective Brain or Spinal Cord Passaging.
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Rabinovich, Roberto D., Lascano, Eduardo F., and Boxaca, Martha C.
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- 1986
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156. Evaluación de intervenciones durante la pandemia COVID-19: desarrollo de un modelo basado en subpoblaciones con distintas tasas de contacto
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Morando, Nicolás, Sanfilippo, Mauricio, Herrero, Francisco, Iturburu, Matías, Torti, Ariel, Gutson, Daniel, Pando, María A., and Rabinovich, Roberto Daniel
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•Los modelos matemáticos permiten evaluar la evolución de la pandemia por SARS-CoV-2.•El modelo desarrollado contempla subpoblaciones con distintas tasas de contactos.•Las predicciones del SEIR-HL son más optimistas que las del SEIR.•El cálculo modificado de R0permite comparar distintas intervenciones.•El modelo propuesto permite una mejor toma de decisiones en salud pública.
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- 2021
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157. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
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Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Tal-Singer, Ruth, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, and Huang, Jeffrey T.J.
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respiratory tract diseases - Abstract
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p
158. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
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Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, Huang, Jeffrey T.J., Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, and Huang, Jeffrey T.J.
- Abstract
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9GsC
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159. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
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Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, Huang, Jeffrey T.J., Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, and Huang, Jeffrey T.J.
- Abstract
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9GsC
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160. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
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Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, Huang, Jeffrey T.J., Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, and Huang, Jeffrey T.J.
- Abstract
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9GsC
- Full Text
- View/download PDF
161. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD
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Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, Huang, Jeffrey T.J., Rabinovich, Roberto A., Miller, Bruce E., Wrobel, Karolina, Ranjit, Kareshma, Williams, Michelle C., Drost,, Ellen, Edwards, Lisa D., Lomas, David A., Rennard, Stephen I., Agustí, Alvar, Tal-Singer, Ruth, Vestbo, Jørgen, Wouters, Emiel F.M., John, Michelle, van Beek, Edwin J.R., Murchison, John T., Bolton, Charlotte E., MacNee, William, and Huang, Jeffrey T.J.
- Abstract
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality. pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic–femoral pulse wave velocity. pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=−0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05). In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.Elastin degradation is a hallmark of emphysema and may have a role in the pathogenesis of atherosclerosis with COPD http://ow.ly/Y9GsC
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162. Adapting, evaluating and implementing pulmonary rehabilitation in Bangladesh
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Habib, G. M. Monsur, Pinnock, Hilary, and Rabinovich, Roberto
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616.2 ,chronic respiratory diseases ,CRD ,Chronic Obstructive Pulmonary Diseases ,COPD ,Pulmonary Impairment After Tuberculosis ,PIAT ,Pulmonary Rehabilitation - Abstract
Introduction: Chronic Respiratory Diseases (CRDs) are increasing worldwide; more than half of the sufferers live in low- and middle-income countries (LMICs). People with CRDs live with troublesome symptoms, especially breathlessness and fatigue, which reduce their exercise capacity and ability to maintain activity levels. This affects quality-of-life, and overall performance, with many people developing co-morbid anxiety and depression. Pulmonary Rehabilitation (PR) aims to reverse the vicious circle of breathlessness, avoidance of activity, muscle weakness, and further increasing inactivity. There is strong evidence (mainly from high-income countries) that PR improves functional exercise capacity and quality of life, and guidelines recommend PR as an integral part of CRDs care. Despite the potential that implementation of PR could reduce the burden of CRDs, it is notably underprovided in LMICs. AIMS AND OBJECTIVES: I aimed to adapt and test the feasibility of a PR programme to be delivered in a low resource setting and initiate strategies for the implementation of this complex intervention in Bangladesh. My objectives were: • Engage relevant stakeholders, explore, and integrate their views. • Conduct a systematic review to synthesise the clinical effectiveness, components, and mode of delivery of PR in low-resource settings. • Identify core components from global PR guidelines. • Adapt PR protocol for implementation in Bangladesh. • Undertake a feasibility study using mixed-method (quantitative and qualitative) research. • With stakeholders, develop and initiate an ongoing implementation strategy for scaling up and delivering PR in Bangladesh. METHODS: The PhD work proceeded in six phases addressing these objectives: Stakeholder engagement: I selected stakeholders according to their interest and influence; conducting seven meetings across the country to engage them in this implementation research programme and to learn about the context. Systematic Review: I reviewed literature systematically following the Cochrane methodology to identify the evidence generated from LMICs on the effectiveness (improvement of functional exercise capacity and health-related quality of life), useable components, and deliverable models of PR services in a low -resource setting. I searched six databases from 1990 to 2018 with a pre-publication forward citation search in 2020. Global Guidelines Recommendations: I reviewed international PR guidelines and identified the key recommended components of PR. I also visited internationally-recognised centres to learn practical techniques. Adapting a PR programme to the Bangladesh context: I mapped each of the recommended components of PR to an approach that could be delivered in a low resource setting and tailored to the Bangladesh context. Feasibility Study: I planned a mixed-methods, before-and-after feasibility study of PR delivered to groups in my community-based clinic in Khulna. The feasibility study was interrupted by the COVID-19 pandemic. The original intention was to conduct an 8-week centre-based PR programme with face-to-face supervised sessions, including exercise and educational programmes. After completing about one-third of the study, this was suspended due to the pandemic. After a delay of three months, I resumed the feasibility study, having adapted the PR programme for home delivery (with Centre-based assessments) in line with national social distancing regulations and the Sponsor's requirements. Quantitative Analysis: I compared pre- and post-measurements of exercise capacity (ESWT: Endurance Shuttle Walking Test) and quality-of-life (CAT: COPD Assessment Test) using T-tests or non-parametric tests according to the distribution of the data. Secondary outcomes included dyspnoea and anxiety/depression. Qualitative data collection and analysis: Interviews with 15 patients, eleven professionals, two hospital/clinic owners cum managers, and three other stakeholders were recorded, transcribed verbatim, and analysed using two approaches: A grounded theory approach explored patients' views on living with CRDs and the acceptability, benefits, challenges, and enablers for PR. A framework approach, using the Normalisation Process Theory (NPT) Toolkit to understand professional/stakeholder' views about implementing PR in clinical practice. Finally, I synthesised the findings from both the quantitative and qualitative methods to answer the objectives of the feasibility study. Develop implementation strategy: I am working with stakeholders to raise awareness meetings, workshops, seminars, and symposiums on PR as a continuous process for the implementation and integration of PR services in routine clinical practice in Bangladesh. Results: Initial stakeholder meetings identified multiple challenges: lack of research evidence on clinical effectiveness in Bangladesh, poor patient health literacy, economic and cultural barriers, widespread exposure to risk factors, and lack of knowledge among health professionals. There is a need to educate professionals (and specifically train PR therapists), involve influential political and religious leaders, and provide accessible services. These broadly align with the policy statement of ATS/ERS with regard to raising awareness and generating evidence on PR in our own context. The systematic review included 13 controlled studies evaluating the effectiveness of PR in LMICs. In most studies, functional exercise capacity and quality of life improved, but 11/13 studies were at high risk of bias. One of the two studies at moderate risk of bias showed no benefit. All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises. Adapted to the setting, low-cost services used limited equipment and typically combined outpatient/centre delivery with a home/community-based service. From global PR guidelines, I developed a matrix of the practical components with a detailed description of each element and models of delivery in various settings. The components recommended in global PR guidelines are typically described for delivery in high-income settings. I, therefore, adapted the components to my local low-resource community-based context to develop a protocol for PR in Bangladesh. The feasibility study commenced as a Centre-based programme before the pandemic. Of 296 patients referred from my practice, 89 (30%) patients participated allocated to one of four unisex groups. Of the 207 (70%) who refused centre-based PR, 107 (52%) preferred home-based, 69 (33%) community-based, and only 32 (15%) declined to participate in the research, citing concern that PR might exacerbate their breathlessness, or impose an extra financial burden. The first group had completed 70% of the sessions, the second group had completed 50% of the sessions; the third and fourth groups had just started their programmes when the study was suddenly suspended due to the COVID-19 pandemic. Adapted for home delivery in the pandemic. Sixty-one patients were referred for PR; 51 participated (mean age 55 years (SD 12); M: F 33:18). Forty-four patients (86%) completed 11 (70%) of the remotely supervised sessions. Forty participants (78%) attended the post-PR assessment at eight weeks. Quantitative Analysis: Functional exercise capacity measured by Endurance Shuttle Walking Test (ESWT) improved by 345 seconds (Minimum Clinically Important Difference (MCID) is 174s). Pre: median (IQR) 291 (119, 989) vs post: 544 (60, 1200); P < 0.0001. Quality-of-life measured by the COPD Assessment Test improved by 7 (MCID is 2), Pre: median (IQR) 16.5 (4, 28) vs post: 7.5 (0, 26); p<0.0001. Patients defined their condition by the symptoms (as opposed to a disease). Some were surprised at being offered an exercise programme that triggered breathlessness (the symptom they were trying to cure). Most patients were concerned about the affordability and availability of the service. Professionals perceived PR as a novel intervention, and were aware of evidence of its effectiveness, but had no personal experience on which to base their opinions. Implementation strategy. Building on the evidence from this PhD, I am working on continuous stakeholder engagement, building awareness, and developing skilled professionals through seminars, symposiums and workshops. Conclusions: PR is an integral part of care of the increasing burden of CRDs. It is effective, deliverable, and has applicable components for our context. The feasibility study demonstrated the acceptability and potential benefits of implementing PR in Bangladesh. Stakeholder engagement, especially with influential groups, is the key to implementation. Improving awareness, developing a skilled workforce, and a cost-effective, affordable and easily accessible PR model are pre-requisites of providing patients with CRDs.
- Published
- 2022
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163. Role of physical activity in daily life in Chronic Obstructive Pulmonary Disease (COPD)
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Mantoani, Leandro Cruz, McKinstry, Brian, MacNee, William, and Rabinovich, Roberto
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616.2 ,COPD ,physical activity ,pulmonary rehabilitation ,telehealth - Abstract
Background: Chronic obstructive pulmonary disease (COPD) is an important common chronic lung condition that is a leading cause of morbidity and mortality worldwide, resulting in a substantial and increasing economic and social burden to health care systems. Physical activity (PA) is the strongest predictor of mortality in this population, playing an important role determining the quality of life in COPD, with better outcomes being reported by those who have higher levels of PA. Therefore, improving PA levels has been considered a key component in the management of patients with COPD. Likewise, it is important to understand the mechanisms that lead to inactivity, as it is to develop accurate methods of measuring PA in this population. Aims of the thesis: 1) To identify and to summarize the interventions able to increase PA levels in patients with COPD; 2) To understand the longitudinal interaction between muscle mass and function and PA levels in COPD; 3) To study the acceptability and the suitability of a new activity monitor (TracMor D - Philips, the Netherlands) for home coaching in daily routine of patients with COPD; and 4) To investigate whether a PA enhancing programme with set targets and feedback would constitute a successful intervention to increase PA levels in patients with COPD attending pulmonary rehabilitation (PR). Methods: To achieve the first aim of the thesis I performed a systematic review summarizing interventional studies that assessed PA as an outcome in patients with COPD. For the second aim, I analysed some multicentric longitudinal data (one year follow-up) on PA and muscle mass/function in COPD. The third aim was achieved with a pilot study I conducted in Edinburgh, where patients with COPD wore three TracMor D in different body places simultaneously with the criterion method (Actigraph GT3x activity monitor) for a week. To accomplish the fourth and main aim of my PhD, I conducted a randomised controlled trial (RCT) where patients with COPD undergoing PR were randomised to either receive PR only or PR plus a PA coaching programme using the TracMor D activity monitor for 12 weeks. Main Results: Study 1: Sixty studies were considered for data extraction in the systematic review. Seven types of intervention with the potential to increase PA levels in patients with COPD were identified. PR programmes with more than 12 weeks of duration and PA coaching programmes with feedback of an activity monitor are promising interventions to increase activity levels in patients with COPD. Overall, the quality of evidence across interventional studies was graded as very low. Study 2: The longitudinal study showed that there were weak correlations between PA levels and muscle strength at baseline (0.19 ≤ r ≤ 0.33 p < 0.001 for all). No correlations were found between changes in PA and muscle strength (-509 [-1295-362] vs -0.4 [-3.5-2.6] - 12 months minus baseline - respectively) and future muscle mass (p > 0.05). Baseline PA levels are related to future muscle strength (0.30 ≤ r ≤ 0.41, p < .0001) but not with muscle mass. Study 3: This study showed that TracMor D had strong correlations with Actigraph GT3x in terms of Kcal consumption in all three positions (necklace, pocket and hip) (0.84 ≥ r < 0.86, p < 0.001 for all). TracMor D was considered comfortable and easy to use at home, receiving a mean usability score of 98 out of 100 maximum points. Study 4: My RCT showed that the proposed PA intervention was effective in changing steps/day (1251 ± 2408 vs control -410 ± 1118, p=0.01), time spent in light activities (21 ± 60 vs -37 ± 55, p=0.004), exercise capacity (99 ± 139 vs 3 ± 83 meters; 85 ± 114 vs 2 ± 62 seconds, p < 0.03 for both) and muscle strength (15 ± 20 vs -5 ± 18, p=0.01) among others when compared to the control group. Conclusions: Strategies focussing specifically on increasing PA and longer PR programmes may have greater impacts on PA levels in COPD. Well-designed clinical trials with objective assessment of PA in patients with COPD are needed. PA levels are not related to one-year changes in muscle mass and muscle strength in patients with COPD. However, higher PA levels at baseline are related to having higher muscle strength at one-year. TracMor D strongly correlated with the criterion method and was highly accepted by patients with COPD in their daily routine, being considered comfortable and easy to use at home. The combination of PR with a physical activity enhancing programme using a PA monitor to set targets and give feedback on activity levels significantly improves PA, exercise capacity, muscle strength, quality of life, and anxiety and depression levels in patients with COPD.
- Published
- 2018
164. The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study
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Stolk Jan, MacNee William, Keatings Vera, Donnelly Seamas C, Millar Ann B, Morgan Kevin, Rabinovich Roberto, Roca Josep, Guetta-Baranes Tamar, Alsaegh Aiman, Lotya Juzer, Daly Leslie, Chappell Sally L, Hiemstra Pieter S, Miniati Massimo, Monti Simonetta, O'Connor Clare M, and Kalsheker Noor
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.
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- 2011
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165. Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population
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Keatings Vera, Donnelly Seamas C, Millar Ann B, Rabinovich Roberto, Roca Josep, Guetta-Baranes Tamar, Morgan Kevin, Daly Leslie, Lotya Juzer, Johnson Simon R, Chappell Sally, Haq Imran, MacNee William, Stolk Jan, Hiemstra Pieter S, Miniati Massimo, Monti Simonetta, O'Connor Clare M, and Kalsheker Noor
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. Methods To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Results Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Conclusions Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.
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- 2010
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166. Exploring the perceptions of patients with chronic respiratory diseases and their insights into pulmonary rehabilitation in Bangladesh.
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Habib GMM, Uzzaman N, Rabinovich R, Akhter S, Ali M, Sultana M, and Pinnock H
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- Humans, Bangladesh, Dyspnea, Exercise, Pulmonary Disease, Chronic Obstructive
- Abstract
Background: Chronic respiratory diseases (CRDs) require holistic management which considers patients' preferences, appropriate pharmacotherapy, pulmonary rehabilitation, and integrated care. We aimed to understand the perceptions of people with CRDs about their condition and pulmonary rehabilitation in Bangladesh., Methods: We conducted semi-structured interviews with a maximum variation sample of people with CRDs who had participated in a feasibility study of pulmonary rehabilitation in 2021/2022. A multidisciplinary team transcribed the interviews verbatim and analysed them in Bengali using a grounded theory approach., Results: We interviewed 15 participants with chronic obstructive pulmonary disease, asthma, or post-tuberculosis. The analysis revealed three themes. The first encompassed understanding CRDs: Patients characterised their condition by the symptoms (e.g. 'Hapani' meaning 'breathlessness') rather than describing a disease entity. Some believed occupation, previous infection, or family history to be a cause. The second theme included perceptions of pulmonary rehabilitation: Exercise was counterintuitive, as it exacerbated the breathlessness symptom that defined their disease. Views varied, though many acknowledged the benefits after a few sessions. Even with home-based programmes, participants described practical barriers to finding time for the sessions and adopted strategies to overcome the challenges. The third theme focused on implementation: Participants highlighted the need for raising awareness of CRDs and the potential of pulmonary rehabilitation in the community, adapting to the local context, and establishing an accessible resourced service., Conclusions: Understanding how patients and their communities perceive their condition and the barriers (both conceptual and logistical) to acceptance is the first step to embedding this highly effective intervention into routine health care services in Bangladesh with potential benefits for the increasing number of people living with CRDs in low- and middle-income countries., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: MH owns the pulmonary rehabilitation clinic in Khulna. HP and MH are co-investigators in the RESPIRE Global Health Unit., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)
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- 2024
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167. Greater male variability in daily energy expenditure develops through puberty.
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Halsey LG, Careau V, Ainslie PN, Alemán-Mateo H, Andersen LF, Anderson LJ, Arab L, Baddou I, Bandini L, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Brage S, Buchowski MS, Butte N, Camps SG, Casper R, Close GL, Colbert LH, Cooper JA, Cooper R, Dabare P, Das SK, Davies PSW, Deb S, Nyström CD, Dietz W, Dugas LR, Eaton S, Ekelund U, Hamdouchi AE, Entringer S, Forrester T, Fudge BW, Gillingham M, Goris AH, Gurven M, Haisma H, Hambly C, Hoffman D, Hoos MB, Hu S, Joonas N, Joosen A, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kriengsinyos W, Kuriyan R, Kushner RF, Lambert EV, Lanerolle P, Larsson CL, Lessan N, Löf M, Martin C, Matsiko E, Meijer GA, Morehen JC, Morton JP, Must A, Neuhouser M, Nicklas TA, Ojiambo RM, Pietilainen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich R, Racette SB, Raichen DA, Ravussin E, Redman L, Reilly JJ, Reynolds R, Roberts S, Rood JC, Samaranayake D, Sardinha LB, Scuitt AJ, Silva AM, Sinha S, Sjödin AM, Stice E, Stunkard A, Urlacher SS, Valencia ME, Valenti G, van Etten LM, Van Mil EA, Verbunt JA, Wells JCK, Wilson G, Wood B, Yoshida T, Zhang X, Murphy-Alford A, Loechl C, Luke A, Pontzer H, Rood J, Sagayama H, Westerterp KR, Wong WW, Yamada Y, and Speakman JR
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- Adolescent, Young Adult, Female, Humans, Male, Adult, Reproduction, Energy Metabolism, Phenotype, Puberty, Sexual Behavior
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There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.
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- 2023
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168. [Evaluation of interventions during the COVID-19 pandemic: development of a model based on subpopulations with different contact rates].
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Morando N, Sanfilippo M, Herrero F, Iturburu M, Torti A, Gutson D, Pando MA, and Rabinovich RD
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- Basic Reproduction Number, Disease Susceptibility epidemiology, Humans, SARS-CoV-2, COVID-19 epidemiology, Pandemics prevention & control
- Abstract
Although multiple attempts have been made to mathematically model the current epidemic of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), few models have been conceived as accessible interactive tools for users from various backgrounds. The goal of this study was to develop a model that took into account the heterogeneity in contact rates within the population and to implement it in an accessible application allowing to estimate the impact of possible interventions based on available information. An extended version of the Susceptible-Exposed-Infected-Resistant (SEIR) model, named SEIR-HL, was developed, assuming a population divided into two subpopulations, with different contact rates. Additionally, a formula for the calculation of the basic reproduction number (R
0 ) for a population divided into n subpopulations was proposed, where the contact rates for each subpopulation can be distinguished according to contact type or context. The predictions made by SEIR-HL were compared to those of SEIR, showing that the heterogeneity in contact rates can dramatically affect the dynamics of simulations, even when run from the same initial conditions and with the same parameters. SEIR-HL was used to predict the effect on the epidemic evolution of the displacement of individuals from high-contact positions to low-contact positions. Lastly, by way of example, SEIR-HL was applied to the analysis of the SARS-CoV-2 epidemic in Argentina and an example of the application of the R0 formula was also developed. Both the SEIR-HL model and an R0 calculator were computerized and made available to the community., (Copyright © 2021 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)- Published
- 2022
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169. Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments.
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Garcia-Aymerich J, Puhan MA, Corriol-Rohou S, de Jong C, Demeyer H, Dobbels F, Erzen D, Frei A, Gimeno-Santos E, Hopkinson NS, Ivanoff N, Karlsson N, Louvaris Z, Polkey MI, Rabinovich RA, Scuri M, Tabberer M, Vogiatzis I, and Troosters T
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- Follow-Up Studies, Forced Expiratory Volume, Humans, Prospective Studies, Pulmonary Disease, Chronic Obstructive rehabilitation, Surveys and Questionnaires, Exercise physiology, Exercise Therapy methods, Exercise Tolerance physiology, Psychometrics methods, Pulmonary Disease, Chronic Obstructive physiopathology, Quality of Life
- Abstract
Background: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation., Objective: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries., Methods: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID., Results: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score., Conclusions: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables., Competing Interests: Competing interests: JG-A reports other from AstraZeneca, other from Esteve, other from Chiesi, other from Menarini, outside the submitted work. SC-R reports personal fees from AstraZeneca, outside the submitted work. DE reports personal fees from Boehringer Ingelheim, outside the submitted work. NI reports personal fees from Almirall, outside the submitted work. NK reports personal fees from AstraZeneca, outside the submitted work. MIP reports personal fees from Philips, grants, personal fees and non-financial support from GSK, during the conduct of the study. MS reports personal fees from Chiesi, outside the submitted work. MT reports personal fees and other from GSK, outside the submitted work. TT reports grants from IMI-JU PROactive grant, during the conduct of the study; other from Boehringer Ingelheim, other from AZ Belgium, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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170. A standard calculation methodology for human doubly labeled water studies.
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Speakman JR, Yamada Y, Sagayama H, Berman ESF, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SGJA, Close GL, Cooper JA, Creasy SA, Das SK, Cooper R, Dugas LR, Ebbeling CB, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Ludwig DS, Martin CK, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl CU, Melanson EL, Luke AH, Pontzer H, Rood J, Schoeller DA, Westerterp KR, and Wong WW
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- Calorimetry, Indirect methods, Deuterium metabolism, Humans, Body Composition physiology, Energy Metabolism physiology, Oxygen Isotopes metabolism, Water
- Abstract
The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO
2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)- Published
- 2021
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171. Engaging with stakeholders in a research programme to promote implementation of pulmonary rehabilitation in Bangladesh: Challenges and opportunities.
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Habib GM, Uzzaman MN, Malik P, Rabinovich R, Uddin A, Alam SR, Williams S, and Pinnock H
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- Bangladesh, Health Plan Implementation, Humans, Biomedical Research organization & administration, Lung Diseases rehabilitation
- Abstract
Competing Interests: Competing interests: GMMH and SMRA lead pulmonary rehabilitation clinics in Bangladesh. The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no further conflicts of interest.
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- 2020
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172. Systematic review of clinical effectiveness, components, and delivery of pulmonary rehabilitation in low-resource settings.
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Habib GMM, Rabinovich R, Divgi K, Ahmed S, Saha SK, Singh S, Uddin A, Uzzaman MN, and Pinnock H
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- Breathing Exercises, Humans, Lung Diseases therapy, Patient Education as Topic, Pulmonary Disease, Chronic Obstructive rehabilitation, Treatment Outcome, Lung Diseases rehabilitation
- Abstract
Pulmonary rehabilitation (PR) is a guideline-recommended multifaceted intervention that improves the physical and psychological well-being of people with chronic respiratory diseases (CRDs), though most of the evidence derives from trials in high-resource settings. In low- and middle-income countries, PR services are under-provided. We aimed to review the effectiveness, components and mode of delivery of PR in low-resource settings. Following Cochrane methodology, we systematically searched (1990 to October 2018; pre-publication update March 2020) MEDLINE, EMBASE, CABI, AMED, PUBMED, and CENTRAL for controlled clinical trials of adults with CRD (including but not restricted to chronic obstructive pulmonary disease) comparing PR with usual care in low-resource settings. After duplicate selection, we extracted data on exercise tolerance, health-related quality of life (HRQoL), breathlessness, included components, and mode of delivery. We used Cochrane risk of bias (RoB) to assess study quality and synthesised data narratively. From 8912 hits, we included 13 studies: 11 were at high RoB; 2 at moderate RoB. PR improved functional exercise capacity in 10 studies, HRQoL in 12, and breathlessness in 9 studies. One of the two studies at moderate RoB showed no benefit. All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises. Low cost services, adapted to the setting, used limited equipment and typically combined outpatient/centre delivery with a home/community-based service. Multicomponent PR programmes can be delivered in low-resource settings, employing a range of modes of delivery. There is a need for a high-quality trial to confirm the positive findings of these high/moderate RoB studies.
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- 2020
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173. ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases.
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Radtke T, Crook S, Kaltsakas G, Louvaris Z, Berton D, Urquhart DS, Kampouras A, Rabinovich RA, Verges S, Kontopidis D, Boyd J, Tonia T, Langer D, De Brandt J, Goërtz YMJ, Burtin C, Spruit MA, Braeken DCW, Dacha S, Franssen FME, Laveneziana P, Eber E, Troosters T, Neder JA, Puhan MA, Casaburi R, Vogiatzis I, and Hebestreit H
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- Chronic Disease, Clinical Protocols, Europe, Humans, Exercise Test, Lung Diseases diagnosis
- Abstract
The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data., Competing Interests: Conflict of interest: T. Radtke reports personal fees for registration and travel/accomodation for conferences from Vifor Pharma, outside of the submitted work. Conflict of interest: S. Crook has nothing to disclose. Conflict of interest: G. Kaltsakas has nothing to disclose. Conflict of interest: G. Louvaris has nothing to disclose. Conflict of interest: D. Berton has nothing to disclose. Conflict of interest: D.S. Urquhart has nothing to disclose. Conflict of interest: A. Kampouras has nothing to disclose. Conflict of interest: R.A. Rabinovich has nothing to disclose. Conflict of interest: S. Verges has nothing to disclose. Conflict of interest: D. Kontopidis is President of the Hellenic Cystic Fibrosis Association. Conflict of interest: J. Boyd reports is an employee of the European Lung Foundation. Conflict of interest: T. Tonia reports acting as ERS Methodologist. Conflict of interest: D. Langer has nothing to disclose. Conflict of interest: J. De Brandt has nothing to disclose. Conflict of interest: Y.M.J. Goërtz has nothing to disclose. Conflict of interest: C. Burton has nothing to disclose. Conflict of interest: M.A. Spruit reports grants and personal fees from Boehringer-Ingelheim and AstraZeneca, personal fees from GSK and Novartis, congress travel support from TEVA, and grants from the Netherlands Lung Foundation, outside the submitted work. Conflict of interest: D.C.W. Braeken has nothing to disclose. Conflict of interest: S. Dacha has nothing to disclose. Conflict of interest: F.M.E. Franssen reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and TEVA, and grants and personal fees from Novartis, outside the submitted work. Conflict of interest: P. Laveneziana reports personal fees from Novartis France and Boehringer France, outside the submitted work. Conflict of interest: E. Eber has nothing to disclose. Conflict of interest: T. Troosters has nothing to disclose. Conflict of interest: J.A Neder has nothing to disclose. Conflict of interest: M.A. Puhan has nothing to disclose. Conflict of interest: R. Casaburi reports that he shares patent US 7927251 B1, relating to a linear treadmill testing protocol, issued to Los Angeles Biomedical Research Institute. Conflict of interest: I. Vogiatzis has nothing to disclose. Conflict of interest: H. Hebestreit reports grants and personal fees from Vertex Pharmaceuticals, grants from Mukoviszidose e.V. (German CF Organization), outside the submitted work; and is the Coordinator of the European Cystic Fibrosis Society Exercise Working Group who discuss exercise testing and organise respective symposia., (Copyright ©ERS 2019.)
- Published
- 2019
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174. Progression of physical inactivity in COPD patients: the effect of time and climate conditions - a multicenter prospective cohort study.
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Boutou AK, Raste Y, Demeyer H, Troosters T, Polkey MI, Vogiatzis I, Louvaris Z, Rabinovich RA, van der Molen T, Garcia-Aymerich J, and Hopkinson NS
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- Aged, Disease Progression, Female, Fitness Trackers, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Respiratory Function Tests, Time Factors, Climate, Exercise Tolerance physiology, Pulmonary Disease, Chronic Obstructive physiopathology, Sedentary Behavior, Walking physiology
- Abstract
Purpose: Longitudinal data on the effect of time and environmental conditions on physical activity (PA) among COPD patients are currently scarce, but this is an important factor in the design of trials to test interventions that might impact on it. Thus, we aimed to assess the effect of time and climate conditions (temperature, day length and rainfall) on progression of PA in a cohort of COPD patients., Patients and Methods: This is a prospective, multicenter, cohort study undertaken as part of the EU/IMI PROactive project, in which we assessed 236 COPD patients simultaneously wearing two activity monitors (Dynaport MiniMod and Actigraph GT3X). A multivariable generalized linear model analysis was conducted to describe the effect of the explanatory variables on PA measures, over three time points (baseline, 6 and 12 months)., Results: At 12 months (n=157; FEV
1 % predicted=57.7±21.9) there was a significant reduction in all PA measures (Actigraph step count (4284±3533 vs 3533±293)), Actigraph moderate- to vigorous-intensity PA ratio (8.8 (18.8) vs 6.1 (15.7)), Actigraph vector magnitude units (374,902.4 (265,269) vs 336,240 (214,432)), MiniMod walking time (59.1 (34.9) vs 56.9 (38.7) mins) and MiniMod PA intensity (0.183 (0) vs 0.181 (0)). Time had a significant, negative effect on most PA measures in multivariable analysis, after correcting for climate factors, study center, age, FEV1 % predicted, 6MWD and other disease severity measures. Rainfall was the only climate factor with a negative effect on most PA parameters., Conclusion: COPD patients demonstrate a significant decrease in PA over 1 year follow-up, which is further affected by hours of rainfall, but not by other climate considerations., Competing Interests: JGA received payments for consulting and lecture fees to her Institution from AstraZeneca and lecture fees from Esteeve and Chiesi, outside the submitted work. MIP received personal fees from Phillips, grants from EU and travel expenses from CBQC, outside the submitted work. TvdM is currently a part-time employee of GSK London. The authors report no other conflicts of interest in this work., (© 2019 Boutou et al.)- Published
- 2019
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175. Systematic review (protocol) of clinical effectiveness and models of care of low-resource pulmonary rehabilitation.
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Habib GMM, Rabinovich R, Divgi K, Ahmed S, Saha SK, Singh S, Uddin A, and Pinnock H
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- Chronic Disease, Developing Countries, Health Resources, Humans, Treatment Outcome, Systematic Reviews as Topic, Respiratory Tract Diseases rehabilitation
- Abstract
More than half of the people with chronic respiratory diseases (CRDs) live in low- and middle-income countries (LMICs). The increasing disability, reduced productivity, associated anxiety and depression from CRDs result in social isolation and economic hardship for patients and their families. Pulmonary rehabilitation (PR) is a guideline-recommended multidisciplinary and multifaceted intervention that improves the physical and psychological condition of people with CRD. However, PR services are underprovided and uptake is poor in LMICs, especially in low-resourced setting. We aim to systematically assess the effectiveness, applicable components and mode of delivery of PR. We will search MEDLINE, EMBASE, CABI, AMED and CENTRAL from January 1990 using a PICOS search strategy (Population: adults with CRD (including chronic obstructive pulmonary disease, post-tuberculosis, remodelled asthma); Intervention: PR; Comparator: usual care; Outcomes: functional exercise capacity and Health-Related Quality-of-Life; Setting: low-resource settings). Two reviewers will independently screen titles/abstracts and full texts for eligibility and extract data from included papers. We will use the Cochrane Risk-of-Bias tool, rating the quality of evidence using GRADE. We will use narrative synthesis to answer our three objectives: What is the effectiveness of PR in low-resource settings? What components are used in effective studies? What models of service delivery are used? This systematic review will inform the potential impact and practical models of low-resource PR for the betterment of patients with CRDs to improve their substantial health-care burden and address poor quality of life.
- Published
- 2019
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176. Smartphone-Based Physical Activity Telecoaching in Chronic Obstructive Pulmonary Disease: Mixed-Methods Study on Patient Experiences and Lessons for Implementation.
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Loeckx M, Rabinovich RA, Demeyer H, Louvaris Z, Tanner R, Rubio N, Frei A, De Jong C, Gimeno-Santos E, Rodrigues FM, Buttery SC, Hopkinson NS, Büsching G, Strassmann A, Serra I, Vogiatzis I, Garcia-Aymerich J, Polkey MI, and Troosters T
- Abstract
Background: Telecoaching approaches can enhance physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD). However, their effectiveness is likely to be influenced by intervention-specific characteristics., Objective: This study aimed to assess the acceptability, actual usage, and feasibility of a complex PA telecoaching intervention from both patient and coach perspectives and link these to the effectiveness of the intervention., Methods: We conducted a mixed-methods study based on the completers of the intervention group (N=159) included in an (effective) 12-week PA telecoaching intervention. This semiautomated telecoaching intervention consisted of a step counter and a smartphone app. Data from a project-tailored questionnaire (quantitative data) were combined with data from patient interviews and a coach focus group (qualitative data) to investigate patient and coach acceptability, actual usage, and feasibility of the intervention. The degree of actual usage of the smartphone and step counter was also derived from app data. Both actual usage and perception of feasibility were linked to objectively measured change in PA., Results: The intervention was well accepted and perceived as feasible by all coaches present in the focus group as well by patients, with 89.3% (142/159) of patients indicating that they enjoyed taking part. Only a minority of patients (8.2%; 13/159) reported that they found it difficult to use the smartphone. Actual usage of the step counter was excellent, with patients wearing it for a median (25th-75th percentiles) of 6.3 (5.8-6.8) days per week, which did not change over time (P=.98). The smartphone interface was used less frequently and actual usage of all daily tasks decreased significantly over time (P<.001). Patients needing more contact time had a smaller increase in PA, with mean (SD) of +193 (SD 2375) steps per day, +907 (SD 2306) steps per day, and +1489 (SD 2310) steps per day in high, medium, and low contact time groups, respectively; P for-trend=.01. The overall actual usage of the different components of the intervention was not associated with change in step count in the total group (P=.63)., Conclusions: The 12-week semiautomated PA telecoaching intervention was well accepted and feasible for patients with COPD and their coaches. The actual usage of the step counter was excellent, whereas actual usage of the smartphone tasks was lower and decreased over time. Patients who required more contact experienced less PA benefits., Trial Registration: ClinicalTrials.gov NCT02158065; http://clinicaltrials.gov/ct2/show/NCT02158065 (Archived by WebCite at http://www.webcitation.org/73bsaudy9)., (©Matthias Loeckx, Roberto A Rabinovich, Heleen Demeyer, Zafeiris Louvaris, Rebecca Tanner, Noah Rubio, Anja Frei, Corina De Jong, Elena Gimeno-Santos, Fernanda M Rodrigues, Sara C Buttery, Nicholas S Hopkinson, Gilbert Büsching, Alexandra Strassmann, Ignasi Serra, Ioannis Vogiatzis, Judith Garcia-Aymerich, Michael I Polkey, Thierry Troosters. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 21.12.2018.)
- Published
- 2018
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177. Role of accelerated aging in limb muscle wasting of patients with COPD.
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Lakhdar R, McGuinness D, Drost EM, Shiels PG, Bastos R, MacNee W, and Rabinovich RA
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- Aged, Case-Control Studies, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16 analysis, Cyclin-Dependent Kinase Inhibitor p18 analysis, Female, Humans, Japan, London, Male, Muscular Atrophy, Quality of Life, Sirtuin 1 analysis, Sirtuins analysis, Telomere, Aging, DNA Repair, Histones analysis, Muscle, Skeletal chemistry, Pulmonary Disease, Chronic Obstructive metabolism
- Abstract
Purpose: Skeletal muscle wasting is an independent predictor of health-related quality of life and survival in patients with COPD, but the complexity of molecular mechanisms associated with this process has not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated aging phenotype in patients with COPD., Patients and Methods: The levels of phosphorylated H2AX (γH2AX), a molecule that promotes DNA repair, were assessed in vastus lateralis biopsies from 10 COPD patients with low fat-free mass index (FFMI; COPD
L ), 10 with preserved FFMI and 10 age- and gender-matched healthy controls. A panel of selected markers for cellular aging processes (CDKN2A/p16ink4a , SIRT1, SIRT6, and telomere length) were also assessed. Markers of oxidative stress and cell damage and a panel of pro-inflammatory and anti-inflammatory cytokines were evaluated. Markers of muscle regeneration and apoptosis were also measured., Results: We observed a decrease in γH2AX expression in COPDL , which occurred in association with a tendency to increase in CDKN2A/p16ink4a , and a significant decrease in SIRT1 and SIRT6 protein levels. Cellular damage and muscle inflammatory markers were also increased in COPDL ., Conclusion: These data are in keeping with an accelerated aging phenotype as a result of impaired DNA repair and dysregulation of cellular homeostasis in the muscle of COPDL . These data indicate cellular degeneration via stress-induced premature senescence and associated inflammatory responses abetted by the senescence-associated secretory phenotype and reflect an increased expression of markers of oxidative stress and inflammation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.- Published
- 2018
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178. Translation to Spanish and Validation of the Specific Saint George's Questionnaire for Idiopathic Pulmonary Fibrosis.
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Capparelli I, Fernandez M, Saadia Otero M, Steimberg J, Brassesco M, Campobasso A, Palacios S, Caro F, Alberti ML, Rabinovich RA, and Paulin F
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- Aged, Female, Humans, Idiopathic Pulmonary Fibrosis blood, Language, Male, Oxygen blood, Pulmonary Diffusing Capacity, Reproducibility of Results, Vital Capacity, Health Surveys, Idiopathic Pulmonary Fibrosis physiopathology, Quality of Life, Translations
- Abstract
Introduction: Interstitial lung disease (ILD) is associated with low exercise tolerance, dyspnea, and decreased health-related quality of life (HRQL). Idiopathic pulmonary fibrosis (IPF) is one of the most prevalent in the group. A specific version of the Saint George's questionnaire (SGRQ-I) has been developed to quantify the HRQL of IPF patients. However, this tool is not currently validated in the Spanish language. The objective was to translate into Spanish and validate the specific Saint George's Respiratory Questionnaire for idiopathic pulmonary fibrosis (SGRQ-I)., Methods: The repeatability, internal consistency and construct validity of the SGRQ-I in Spanish were analyzed after a backtranslation process., Results: In total, 23 outpatients with IPF completed the translated SGRQ-I twice, 7 days apart. Repeatability was studied, revealing good concordance in test-retest with an ICC (interclass correlation coefficient) of 0.96 (P<.001). Internal consistency was good for different questionnaire items (Cronbach's alpha of 0.9 including and 0.81 excluding the total value) (P<.001). The total score of the questionnaire showed good correlation with forced vital capacity FVC% (r=-0.44; P=.033), diffusing capacity of the lungs for carbon monoxide (DL
CO %) (r=-0.55; P=.011), partial pressure of oxygen in arterial blood PaO2 (r=-0.44; P=.036), Medical Research Council Dyspnea scale (r=-0.65; P<.001), and number of steps taken in 24hours (r=-0.47; P=.024)., Conclusions: The Spanish version of SGRQ-Ideveloped by our group shows good internal consistency, reproducibility and validity, so it can be used for the evaluation of quality of life (QOL) in IPF patients., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)- Published
- 2018
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179. Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD.
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Rodríguez DA, Kortianou EA, Alison JA, Casas A, Giavedoni S, Barberan-Garcia A, Arbillaga A, Vilaró J, Gimeno-Santos E, Vogiatzis I, Rabinovich R, and Roca J
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- Aged, Area Under Curve, Colombia, Disease Progression, Europe, Female, Forced Expiratory Volume, Humans, Kaplan-Meier Estimate, Linear Models, Logistic Models, Male, Middle Aged, New South Wales, Odds Ratio, Predictive Value of Tests, Prospective Studies, Pulmonary Disease, Chronic Obstructive diagnosis, ROC Curve, Recovery of Function, Time Factors, Exercise Tolerance, Heart Rate, Lung physiopathology, Pulmonary Disease, Chronic Obstructive physiopathology, Walk Test
- Abstract
Introduction: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR
1 ) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD)., Methods: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1 ). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months., Results: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1 , p = 0.004 [log-rank test])., Conclusions: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients.- Published
- 2017
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180. Can health status questionnaires be used as a measure of physical activity in COPD patients?
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Demeyer H, Dueñas-Espín I, De Jong C, Louvaris Z, Hornikx M, Gimeno-Santos E, Loeckx M, Vogiatzis I, Janssens W, Hopkinson NS, Rabinovich RA, Karlsson N, Garcia-Aymerich J, and Troosters T
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- Aged, Female, Humans, Male, Exercise, Health Status, Pulmonary Disease, Chronic Obstructive physiopathology, Surveys and Questionnaires
- Published
- 2016
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181. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement.
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Puente-Maestu L, Palange P, Casaburi R, Laveneziana P, Maltais F, Neder JA, O'Donnell DE, Onorati P, Porszasz J, Rabinovich R, Rossiter HB, Singh S, Troosters T, and Ward S
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- Advisory Committees, Breath Tests, Carbon Dioxide, Dyspnea etiology, Europe, Humans, Hypertension, Pulmonary complications, Hypertension, Pulmonary physiopathology, Hypertension, Pulmonary therapy, Inspiratory Capacity, Oxygen Consumption, Pulmonary Disease, Chronic Obstructive complications, Pulmonary Disease, Chronic Obstructive physiopathology, Pulmonary Disease, Chronic Obstructive therapy, Pulmonary Medicine, Pulmonary Ventilation, Reproducibility of Results, Respiratory Tract Diseases complications, Respiratory Tract Diseases physiopathology, Societies, Medical, Walking, Dyspnea physiopathology, Exercise Test methods, Exercise Tolerance, Outcome Assessment, Health Care, Respiratory Tract Diseases therapy
- Abstract
This document reviews 1) the measurement properties of commonly used exercise tests in patients with chronic respiratory diseases and 2) published studies on their utilty and/or evaluation obtained from MEDLINE and Cochrane Library searches between 1990 and March 2015.Exercise tests are reliable and consistently responsive to rehabilitative and pharmacological interventions. Thresholds for clinically important changes in performance are available for several tests. In pulmonary arterial hypertension, the 6-min walk test (6MWT), peak oxygen uptake and ventilation/carbon dioxide output indices appear to be the variables most responsive to vasodilators. While bronchodilators do not always show clinically relevant effects in chronic obstructive pulmonary disease, high-intensity constant work-rate (endurance) tests (CWRET) are considerably more responsive than incremental exercise tests and 6MWTs. High-intensity CWRETs need to be standardised to reduce interindividual variability. Additional physiological information and responsiveness can be obtained from isotime measurements, particularly of inspiratory capacity and dyspnoea. Less evidence is available for the endurance shuttle walk test. Although the incremental shuttle walk test and 6MWT are reliable and less expensive than cardiopulmonary exercise testing, two repetitions are needed at baseline. All exercise tests are safe when recommended precautions are followed, with evidence suggesting that no test is safer than others., (Copyright ©ERS 2016.)
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- 2016
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182. Effect of downsampling and compressive sensing on audio-based continuous cough monitoring.
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Casaseca-de-la-Higuera P, Lesso P, McKinstry B, Pinnock H, Rabinovich R, McCloughan L, and Monge-Álvarez J
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- Algorithms, Compressive Strength, Female, Humans, Male, Sensitivity and Specificity, Cough diagnosis
- Abstract
This paper presents an efficient cough detection system based on simple decision-tree classification of spectral features from a smartphone audio signal. Preliminary evaluation on voluntary coughs shows that the system can achieve 98% sensitivity and 97.13% specificity when the audio signal is sampled at full rate. With this baseline system, we study possible efficiency optimisations by evaluating the effect of downsampling below the Nyquist rate and how the system performance at low sampling frequencies can be improved by incorporating compressive sensing reconstruction schemes. Our results show that undersampling down to 400 Hz can still keep sensitivity and specificity values above 90% despite of aliasing. Furthermore, the sparsity of cough signals in the time domain allows keeping performance figures close to 90% when sampling at 100 Hz using compressive sensing schemes.
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- 2015
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183. Physiological response during activity programs using Wii-based video games in patients with cystic fibrosis (CF).
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del Corral T, Percegona J, Seborga M, Rabinovich RA, and Vilaró J
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- Adolescent, Body Mass Index, Child, Exercise Test, Female, Forced Expiratory Volume, Heart Rate, Humans, Male, Oxygen Consumption, Physical Exertion, Cystic Fibrosis physiopathology, Cystic Fibrosis rehabilitation, Exercise physiology, Video Games
- Abstract
Unlabelled: Patients with cystic fibrosis (CF) are characterized by an abnormal ventilation response that limits the exercise capacity. Exercise training increases exercise capacity, decreases dyspnea and improves health-related quality of life in CF. Adherence to pulmonary rehabilitation programs is a key factor to guarantee optimal benefits and a difficult goal in this population. The aim of this study was to determine the physiological response during three Nintendo Wii™ video game activities (VGA) candidates to be used as training modalities in patients with CF., Method: 24 CF patients (age 12.6±3.7 years; BMI 18.8±2.9kgm(-2); FEV1 93.8±18.8%pred) were included. All participants performed, on two separate days, 3 different VGA: 1) Wii Fit Plus (Wii-Fit); 2) Wii Active (Wii-Acti), and 3) Wii Family Trainer (Wii-Train), in random order during 5min. The obtained results were compared with the 6-min walk test (6MWT). The physiological variables [oxygen uptake (VO2), minute ventilation (VE), and heart rate (HR)] were recorded using a portable metabolic analyzer., Results: During all VGA and 6MWT, VO2 reached a plateau from the 3rd min. Compared with the 6MWT (1024.2±282.2mLm(-1)), Wii-Acti (1232.2±427.2mLm(-1)) and Wii-Train (1252.6±360.2mLm(-1)) reached higher VO2 levels during the last 3min (p<0.0001 in both cases), while Wii-Fit (553.8±113.2mLm(-1)) reached significantly lower levels of VO2 (p<0.001). Similar effects were seen for the ventilatory volume (VE). No differences in dyspnea and oxygen saturation were seen between the different modalities. All patients were compliant with all three Wii™ modalities., Conclusion: Active video game are well tolerated by patients with CF. All the modalities evaluated imposed a constant load but were associated with different physiological responses reflecting the different intensities imposed. Wii-Acti and Wii-Train impose a significantly high metabolic demand comparable to the 6MWT. Further research is needed to evaluate the effects of VGA as a training program to increase exercise capacity for CF patients., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
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184. The PROactive innovative conceptual framework on physical activity.
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Dobbels F, de Jong C, Drost E, Elberse J, Feridou C, Jacobs L, Rabinovich R, Frei A, Puhan MA, de Boer WI, van der Molen T, Williams K, Pinnock H, Troosters T, Karlsson N, Kulich K, and Rüdell K
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- Aged, Europe, Female, Focus Groups, Humans, Internationality, Male, Middle Aged, Patient Participation, Phenotype, Psychometrics, Pulmonary Disease, Chronic Obstructive psychology, Reproducibility of Results, Research Design, Self Report, Surveys and Questionnaires, Motor Activity, Pulmonary Disease, Chronic Obstructive physiopathology
- Abstract
Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what "physical activity" means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients' perspective. The PROactive PRO instruments' content validity represents the pivotal basis for empirically based item reduction and validation., (©ERS 2014.)
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- 2014
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185. Determinants and outcomes of physical activity in patients with COPD: a systematic review.
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Gimeno-Santos E, Frei A, Steurer-Stey C, de Batlle J, Rabinovich RA, Raste Y, Hopkinson NS, Polkey MI, van Remoortel H, Troosters T, Kulich K, Karlsson N, Puhan MA, and Garcia-Aymerich J
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- Humans, Prognosis, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive mortality, Quality of Life, Motor Activity, Pulmonary Disease, Chronic Obstructive physiopathology
- Abstract
Background: The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD., Methods: We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence., Results: 86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence., Conclusions: Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2014
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186. Neuromuscular electrical stimulation prevents muscle function deterioration in exacerbated COPD: a pilot study.
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Giavedoni S, Deans A, McCaughey P, Drost E, MacNee W, and Rabinovich RA
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- Aged, Feasibility Studies, Female, Humans, Leg, Male, Muscle Strength physiology, Muscle, Skeletal physiology, Pilot Projects, Treatment Outcome, Electric Stimulation Therapy methods, Muscular Diseases prevention & control, Pulmonary Disease, Chronic Obstructive rehabilitation
- Abstract
Purpose: COPD is a condition with systemic effects of which peripheral muscle dysfunction is a prominent contributor to exercise limitation, health related quality of life (HRQoL) impairment, and is an independent predictor of morbidity and mortality. Pulmonary rehabilitation (PR) is a successful strategy to improve exercise tolerance and HRQoL through the improvement of muscle function in patients with stable COPD or early after severe exacerbations of COPD (SECOPD). However, muscle function further deteriorates during SECOPD before early PR programmes commence. We aimed to investigate the feasibility and efficacy of quadriceps neuromuscular electrical stimulation (NMES) applied during a SECOPD to prevent muscle function deterioration., Methods: We have conducted a pilot study in eleven COPD patients (FEV(1) 41.3 ± 5.6 % pred) admitted to hospital with a SECOPD. We randomly allocated one leg to receive NMES (once a day for 14 days) with the other leg as a control (non-stimulated leg). We measured the change in quadriceps maximal voluntary contraction (ΔQMVC) as the main outcome., Results: Mean quadriceps muscle strength decreased in control legs (ΔQMVC -2.9 ± 5.3 N, p = ns) but increased in the stimulated legs (ΔQMVC 19.2 ± 6.1 N, p < 0.01). The difference in ΔQMVC between groups was statistically significant (p < 0.05). The effect of NMES was directly related to the stimulation intensity (∑mA) applied throughout the 14 sessions (r = 0.76, p < 0.01). All patients tolerated NMES without any side effects., Conclusions: NMES is a feasible and effective treatment to prevent quadriceps muscle strength derangement during severe exacerbations of COPD and may be used to compliment early post-exacerbation pulmonary rehabilitation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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187. Validity of activity monitors in health and chronic disease: a systematic review.
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Van Remoortel H, Giavedoni S, Raste Y, Burtin C, Louvaris Z, Gimeno-Santos E, Langer D, Glendenning A, Hopkinson NS, Vogiatzis I, Peterson BT, Wilson F, Mann B, Rabinovich R, Puhan MA, and Troosters T
- Subjects
- Chronic Disease, Databases, Factual, Energy Metabolism, Exercise Test instrumentation, Exercise Test methods, Humans, Running, Monitoring, Physiologic instrumentation, Monitoring, Physiologic methods, Motor Activity
- Abstract
The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n=118), with few carried out in patients with chronic diseases (n=16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (-12.07 (95%CI; -18.28 to -5.85) %) compared to triaxial (-6.85 (95%CI; -18.20 to 4.49) %, p=0.37) and were statistically significantly less accurate than multisensor devices (-3.64 (95%CI; -8.97 to 1.70) %, p<0.001). TEE was underestimated during slow walking speeds in 69% of the lab validation studies compared to 37%, 30% and 37% of the studies during intermediate, fast walking speed and running, respectively. The high level of heterogeneity in the validation studies is only partly explained by the type of activity monitor and the activity monitor outcome. Triaxial and multisensor devices tend to be more valid monitors. Since activity monitors are less accurate at slow walking speeds and information about validated activity monitors in chronic disease populations is lacking, proper validation studies in these populations are needed prior to their inclusion in clinical trials.
- Published
- 2012
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188. Systemic elastin degradation in chronic obstructive pulmonary disease.
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Maclay JD, McAllister DA, Rabinovich R, Haq I, Maxwell S, Hartland S, Connell M, Murchison JT, van Beek EJ, Gray RD, Mills NL, and Macnee W
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- Aged, Biopsy, Disease Progression, Elastin metabolism, Enzyme Precursors biosynthesis, Enzyme Precursors genetics, Forced Expiratory Volume, Gene Expression Regulation, Humans, Immunohistochemistry, Male, Matrix Metalloproteinase 9 biosynthesis, Matrix Metalloproteinase 9 genetics, Middle Aged, Polymerase Chain Reaction, Pulmonary Disease, Chronic Obstructive genetics, Pulmonary Disease, Chronic Obstructive physiopathology, Respiratory Function Tests, Skin pathology, Smoking adverse effects, Smoking metabolism, Elastin genetics, Pulmonary Disease, Chronic Obstructive metabolism, RNA, Messenger genetics, Skin metabolism
- Abstract
Background: Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation., Objectives: To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin., Methods: The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning., Results: Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p=0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and was also associated with increased skin elastin degradation (r=0.62, p<0.001 and r=0.47, p=0.01, respectively). In the entire cohort of ex-smokers, cutaneous elastin degradation was associated with emphysema severity, FEV(1) and pulse wave velocity., Conclusions: Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.
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- 2012
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189. Similar gene expression profiles in smokers and patients with moderate COPD.
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Llinàs L, Peinado VI, Ramon Goñi J, Rabinovich R, Pizarro S, Rodriguez-Roisin R, Barberà JA, and Bastos R
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- Aged, Chemokines genetics, Cytokines genetics, Female, Forced Expiratory Volume, Humans, Male, Matrix Metalloproteinases genetics, Middle Aged, Platelet-Derived Growth Factor genetics, RNA, Messenger analysis, Gene Expression Profiling, Pulmonary Disease, Chronic Obstructive metabolism, Smoking metabolism
- Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by multiple cellular and structural changes affecting the airways, lung parenchyma and vasculature, some of which are also identified in smokers without COPD. The molecular mechanisms underlying these changes remain poorly understood. With the aim of identifying mediators potentially implicated in the pathogenic processes that occur in COPD and their potential relationship with cigarette smoking, we evaluated the mRNA expression of genes involved in inflammation, tissue remodeling and vessel maintenance. Lung tissue samples were obtained from 60 patients who underwent lung resection (nonsmokers, n=12; smokers, n=12; and moderate COPD, n=21) or lung transplant (severe-to-very severe COPD, n=15). PCR arrays containing 42 genes coding for growth factors/receptors, cytokines, metalloproteinases, adhesion molecules, and vessel maintenance mediators were used. Smoking-induced changes include the up-regulation of inflammatory genes (IL-1β, IL-6, IL-8, CCL2, and CCL8) and the decreased expression of growth factor/receptor genes (BMPR2, CTGF, FGF1, KDR and TEK) and genes coding for vessel maintenance factors (EDNRB). All these genes exhibited a similar profile in moderate COPD patients. The up-regulation of MMP1 and MMP9 was the main change associated with COPD. Inflammatory genes as well as the endothelial selectin gene (SELE) were down-regulated in patients with more severe COPD. Clustering analysis revealed a closer relationship between moderate COPD and smokers than between both subsets of COPD patients for this selected set of genes. The study reveals striking similarities between smokers and COPD patients with moderate disease emphasizing the crucial role of cigarette smoking in the genesis of these changes, and provides additional evidence of the involvement of the matrix metalloproteinase's in the remodeling process of the lung in COPD., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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190. Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.
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Haq I, Chappell S, Johnson SR, Lotya J, Daly L, Morgan K, Guetta-Baranes T, Roca J, Rabinovich R, Millar AB, Donnelly SC, Keatings V, MacNee W, Stolk J, Hiemstra PS, Miniati M, Monti S, O'Connor CM, and Kalsheker N
- Subjects
- Aged, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Middle Aged, Severity of Illness Index, Matrix Metalloproteinase 1 genetics, Matrix Metalloproteinase 12 genetics, Matrix Metalloproteinase 9 genetics, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Background: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease--antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies., Methods: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history., Results: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV., Conclusions: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.
- Published
- 2010
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- View/download PDF
191. Centrifugation improves the detection of HIV-1 p24 antigen in plasma from children born to mothers infected with HIV-1.
- Author
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dos Ramos Farías MS, Garcia MN, Dilernia D, Rabinovich RD, and Avila MM
- Subjects
- Adult, Female, Humans, Infant, Infant, Newborn, Mothers, Sensitivity and Specificity, Young Adult, Centrifugation, HIV Core Protein p24 blood, HIV Infections diagnosis, HIV-1 isolation & purification, Infant, Newborn, Diseases virology, Plasma virology
- Abstract
Detection of HIV proteins and/or nucleic acids is necessary for the diagnosis of perinatal HIV infection. Despite its low sensitivity, detection of p24 antigen in plasma is a simple and economic method for the diagnosis of HIV in exposed children. The aim of this study was to improve the sensitivity of detection of p24 using centrifugation of plasma. Forty-seven selected stored samples from 37 children (23 infected, 14 uninfected, median age of 137 days) were examined. Plasma samples (volume 0.3-1.5 ml) were defrosted, centrifuged at 23,500 x g at 4 degrees C for 60 min and determination of p24 was carried out in the resuspended pellet (0.12 ml). In 32 plasma samples from infected children, p24 was found originally in 6 (18.7%) and resulted positive in 24 (75%) pellets. When only one sample per child was considered, sensitivity was significantly higher in pellets, 3/23 uncentrifuged plasma samples and 15/23 pellets (McNemar Test, p<0.001). Specificity was 100%. The absorbance/cut-off ratio was always higher in the pellets from positive children (p=0.028). Plasma samples with volumes of 1 ml or more achieved a higher sensitivity (91.7% vs. 36.4%, p=0.009). Centrifugation of plasma samples prior to determination of p24 in pediatric patients resulted in a significant increase in sensitivity.
- Published
- 2009
- Full Text
- View/download PDF
192. Update in chronic obstructive pulmonary disease 2008.
- Author
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Maclay JD, Rabinovich RA, and MacNee W
- Subjects
- Case-Control Studies, Clinical Trials as Topic, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide genetics, Pulmonary Disease, Chronic Obstructive genetics, Pulmonary Disease, Chronic Obstructive physiopathology, Pulmonary Disease, Chronic Obstructive therapy
- Published
- 2009
- Full Text
- View/download PDF
193. [New argentine consensus of respiratory rehabilitation 2008].
- Author
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Sívori M, Almeida M, Benzo R, Boim C, Brassesco M, Callejas O, Capparelli I, Conti E, Díaz M, Draghi J, Franco J, Gando S, Giuliano G, Guida R, Jolly E, Pessolano F, Rabinovich R, Ratto P, Rhodius E, Saadia M, Salvado A, Sobrino E, and Victorio C
- Subjects
- Argentina, Disability Evaluation, Forms and Records Control, Humans, Patient Education as Topic, Quality of Life, Exercise Therapy standards, Exercise Tolerance physiology, Pulmonary Disease, Chronic Obstructive rehabilitation
- Abstract
Respiratory rehabilitation (RR) is a multidisciplinary program of care for patients with chronic respiratory impairment, individually tailored, designed to optimize physical and social performance and patient autonomy. It is particularly indicated in chronic obstructive pulmonary disease (COPD) patients with exercise intolerance. The objectives of respiratory rehabilitation are: reduction in symptoms and exercise intolerance, improvement of health-related quality of life, and reduction of health costs. A group of neumonologists, nutritionists and physical therapists performed a systematic review of the evidence in RR to update previous local guidelines. Inclusion and exclusion criteria, guidelines for initial evaluation and follow up and resources needed are defined. Training characteristics are recommended regarding frequency of the visits, intensity, progression and duration of the exercise training. Aerobic training was recommended for lower limb (1A), upper limb (1B). Strength training must be added (1B). Respiratory muscle training and other physiotherapy techniques were recommended only for specific patients (1C). In addition recommendations have been made for educational objectives of the program including smoking cessation, nutritional and psychological support. The positive impact of RR on reductions of health care costs and reductions on hospitalizations (Evidence A) and mortality (Evidence B) were analized. Respiratory rehabilitation is a key component in the modern treatment of COPD patients. This consensus statement was prepared based on the most recent scientific evidence and adjusted to the local environment with the aim of being implemented nationally.
- Published
- 2008
194. Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index.
- Author
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Rabinovich RA, Ardite E, Mayer AM, Polo MF, Vilaró J, Argilés JM, and Roca J
- Subjects
- Aged, Chromatography, High Pressure Liquid, Humans, Male, Middle Aged, Oxidation-Reduction, Oxidative Stress physiology, Pulmonary Disease, Chronic Obstructive physiopathology, Body Mass Index, Exercise physiology, Glutathione metabolism, Muscle, Skeletal metabolism, Pulmonary Disease, Chronic Obstructive metabolism
- Abstract
Background: A physiological increase in muscle glutathione after training is not seen in patients with chronic obstructive pulmonary disease (COPD), indicating abnormal peripheral muscle adaptations to exercise., Objective: We hypothesized that oxidative stress is primarily associated with low body mass index (BMI)., Methods: Eleven patients with preserved BMI (BMI(N): 28.2 +/- 1.2 kg.m(-2)), 9 patients with low BMI (BMI(L): 19.7 +/- 0.60 kg.m(-2)) and 5 age-matched controls (26.5 +/- 0.9 kg.m(-2)) were studied before and after 8 weeks of high-intensity endurance training. Reduced glutathione (GSH) and gamma-glutamyl cysteine synthase heavy-subunit chain mRNA expression (gammaGCS-HS mRNA) were measured in the vastus lateralis., Results: After training, exercise capacity increased (DeltaVO(2)PEAK, 13 +/- 5.2%; 10 +/- 5.6% and 15 +/- 4.3% in BMI(L), BMI(N) and controls, respectively; p < 0.05 each). GSH levels decreased in BMI(L) (from 5.2 +/- 0.7 to 3.7 +/- 0.8 nmol/mg protein, DeltaGSH -1.5 +/- 0.7 nmol/mg protein, p < 0.05); no changes were seen in BMI(N) (from 5.4 +/- 0.7 to 6.7 +/- 0.9 nmol/mg protein, DeltaGSH 1.3 +/- 0.9 nmol/mg protein), whereas GSH markedly increased in controls (from 4.6 +/- 1 to 8.7 +/- 0.4 nmol/mg protein, DeltaGSH 4.1 +/- 1 nmol/mg protein, p < 0.01). DeltaGSH in BMI(L) was different from DeltaGSH in BMI(N) and controls (p < 0.05, each). Consistent changes were observed in gammaGCS-HS mRNA expression., Conclusions: GSH depletion after training in BMI(L) may suggest that oxidative stress plays a key role in muscle wasting in COPD patients.
- Published
- 2006
- Full Text
- View/download PDF
195. Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.
- Author
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Chappell S, Daly L, Morgan K, Guetta Baranes T, Roca J, Rabinovich R, Millar A, Donnelly SC, Keatings V, MacNee W, Stolk J, Hiemstra P, Miniati M, Monti S, O'Connor CM, and Kalsheker N
- Subjects
- Aged, Alleles, Case-Control Studies, Exons genetics, Female, Gene Frequency, Humans, Linkage Disequilibrium genetics, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Risk Factors, Genetic Predisposition to Disease, Haplotypes, Pulmonary Disease, Chronic Obstructive genetics, alpha 1-Antitrypsin genetics
- Abstract
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. While cigarette smoking is a major cause of COPD, only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role. To detect cryptic genetic variants that might contribute to disease, we identified 15 SNP haplotype tags from high-density SNP maps of the two genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted so far. For SERPINA1, six newly identified haplotypes with a common backbone of five SNPs were found to increase the risk of disease by six- to 50-fold, the highest risk of COPD reported to date. In contrast, no haplotype associations for SERPINA3 were identified., (2005 Wiley-Liss, Inc.)
- Published
- 2006
- Full Text
- View/download PDF
196. Encouraged 6-min walking test indicates maximum sustainable exercise in COPD patients.
- Author
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Casas A, Vilaro J, Rabinovich R, Mayer A, Barberà JA, Rodriguez-Roisin R, and Roca J
- Subjects
- Aged, Analysis of Variance, Humans, Male, Middle Aged, Oxygen Consumption, Respiratory Function Tests, Exercise Test methods, Exercise Tolerance physiology, Pulmonary Disease, Chronic Obstructive physiopathology, Walking physiology
- Abstract
Study Objectives: In patients with moderate-to-severe COPD, an encouraged 6-min walking test (6MWT) is a high-intensity submaximal exercise protocol that shows an oxygen uptake (Vo(2)) plateau after the third minute of the test. This last feature prompted the hypothesis that self-paced walking speed is set to achieve "maximal" sustainable Vo(2), namely "critical power" or "critical speed.", Patients and Methods: Eight patients with moderate-to-severe COPD (mean age, 68 +/- 7 years [+/- SD]; FEV(1), 50 +/- 13% predicted; Pao(2), 69 +/- 8 mm Hg) underwent the following tests on different days in order: (1) encouraged 6MWT; (2) standard incremental shuttle test to identify peak walking speed; (3) four different high-intensity, constant walking speed tests to exhaustion to calculate critical walking speed; and (4) timed walking test at critical walking speed (CWS) to examine sustainability of the exercise., Results: 6MWT and CWS showed similar results (mean of last 3 min): Vo(2) (1,605 +/- 304 mL/min vs 1,584 +/- 319 mL/min), minute ventilation (47 +/- 12 L/min vs 48 +/- 11 L/min), respiratory exchange ratio (0.89 +/- 0.1 vs 0.90 +/- 0.1), heart rate (130 +/- 18 beats/min vs 131 +/- 16 beats/min), Borg dyspnea score (5.4 +/- 1.3 vs 5.5 +/- 2.4), and walking speed (1.49 +/- 0.1 m/s vs 1.44 +/- 0.1 m/s, respectively)., Conclusion: This study supports that 6MWT indicates maximum sustainable exercise that might be related with its predictive value in COPD patients.
- Published
- 2005
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197. Measles susceptibility in haemodialysis patients in Argentina.
- Author
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Simon M, Baumeister E, Campos AM, Savy V, Martinez R, Perez Loredo J, and Rabinovich RD
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Argentina epidemiology, Disease Susceptibility epidemiology, Female, Humans, Incidence, Kidney Failure, Chronic diagnosis, Male, Measles prevention & control, Middle Aged, Prognosis, Prospective Studies, Renal Dialysis methods, Risk Assessment, Sex Distribution, Vaccination methods, Kidney Failure, Chronic therapy, Measles epidemiology, Measles Vaccine administration & dosage, Renal Dialysis adverse effects
- Published
- 2004
- Full Text
- View/download PDF
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