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1.  Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease 
Background
Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.
Methods
We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.
Results
Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).
Conclusion
Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.
doi:10.1186/1471-2466-9-11
PMCID: PMC2670813  PMID: 19344528
2.  Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers 
Background
Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.
Methods
We measured the levels of leptin, tumor necrosis factor alpha (TNF-α) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.
Results
In plasma of COPD patients, leptin was inversely correlated with TNF-α and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-α. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-α were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.
Conclusion
Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.
doi:10.2147/JIR.S19523
PMCID: PMC3218742  PMID: 22096369
COPD; smokers; inflammation; leptin; neutrophils
3.  Relation of Leptin, Ghrelin and Inflammatory Cytokines with Body Mass Index in Pulmonary Tuberculosis Patients with and without Type 2 Diabetes Mellitus 
PLoS ONE  2013;8(11):e80122.
Background
Pulmonary tuberculosis (TB) patients often suffer from anorexia and poor nutrition, causing weight loss. The peptide hormones leptin and its counterpart ghrelin, acting in the regulation of food intake and fat utilization, play an important role in nutritional balance. This study aimed to investigate the association of blood concentrations of leptin, ghrelin and inflammatory cytokines with body mass index (BMI) in TB patients with and without type 2 diabetes mellitus (T2DM).
Methods
BMI, biochemical parameters and plasma levels of leptin, ghrelin and inflammatory cytokines were measured before the start of treatment in 27 incident TB patients with T2DM, 21 TB patients and 23 healthy subjects enrolled in this study.
Results
The levels of leptin were significantly higher in TB patients (35.2±19.1 ng/ml) than TB+T2DM (12.6±6.1 ng/ml) and control (16.1±11.1 ng/ml) groups. The level of ghrelin was significantly lower in TB (119.9±46.1 pg/ml) and non-significantly lower in TB+T2DM (127.7±38.6 pg/ml) groups than control (191.6±86.5 pg/ml) group. The levels of TNF-α were higher, while IFN-γ and IL-6 levels were lower in patients than in the control group. Leptin showed a negative correlation with BMI in TB (r=-0.622, p<0.05) and TB+T2DM (r= -0.654, p<0.05) groups, but a positive correlation with BMI in the control group (r=0.521, p<0.05). Contrary ghrelin showed a positive correlation with BMI in TB (r=0.695, p<0.05) and TB+T2DM (r= 0.199, p>0.05) groups, but negative correlation with BMI in the control (r=-0.693, p<0.05) group. Inflammatory cytokines were poorly correlated with BMI in this study. Only IFN-γ showed a significant negative correlation with BMI in the control group (r=-0.545, p<0.05).
Conclusions
This study may suggest that possible abnormalities in ghrelin and leptin regulation (high levels of leptin and low levels of ghrelin) may be associated with low BMI and may account for the poor nutrition associated with TB and TB+T2DM.
doi:10.1371/journal.pone.0080122
PMCID: PMC3832650  PMID: 24260344
4.  Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease 
Metabolism: clinical and experimental  2011;60(10):1449-1455.
Objective
The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Changes in protein metabolism and systemic inflammation may contribute to increased resting energy expenditure (REE) in COPD, leading to an energy imbalance and loss of fat and fat-free mass. The objective of this study was to determine first whether REE was increased in patients with COPD and second, whether this was associated with increased protein turnover and/or systemic inflammation.
Materials/Methods
REE was determined using indirect calorimetry in fourteen stable outpatients with severe COPD (seven with low and seven with preserved body mass indices) and seven healthy controls. Endogenous leucine flux, leucine oxidation, and non-oxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis were measured using intravenous infusions of 13C-bicarbonate and 1-13C-leucine. Total body water, from which fat-free mass and fat mass were calculated, was determined using an intravenous bolus of deuterated water. Plasma markers of systemic inflammation were also measured.
Results
As a group, subjects with COPD had increased REE adjusted for fat-free mass (p<0.001) and faster rates of endogenous leucine flux (p=0.006) and non-oxidative leucine disposal (p=0.002) compared with controls. There was a significant correlation between REE and both endogenous leucine flux (p=0.02) and non-oxidative leucine disposal (p=0.008). Plasma concentrations of the inflammatory markers C-reactive protein and interleukin-6 were not different between COPD subjects and controls.
Conclusions
Increased rates of protein turnover are associated with increased REE and loss of fat-free mass in COPD.
doi:10.1016/j.metabol.2011.02.013
PMCID: PMC3176951  PMID: 21550084
leucine; inflammation; weight loss
5.  Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this health technology assessment was to determine the effectiveness, cost-effectiveness, and safety of long-term oxygen therapy (LTOT) for chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Oxygen therapy is used in patients with COPD with hypoxemia, or very low blood oxygen levels, because they may have difficulty obtaining sufficient oxygen from inspired air.
Technology
Long-term oxygen therapy is extended use of oxygen. Oxygen therapy is delivered as a gas from an oxygen source. Different oxygen sources are: 1) oxygen concentrators, electrical units delivering oxygen converted from room air; 2) liquid oxygen systems, which deliver gaseous oxygen stored as liquid in a tank; and 3) oxygen cylinders, which contain compressed gaseous oxygen. All are available in portable versions. Oxygen is breathed in through a nasal cannula or through a mask covering the mouth and nose. The treating clinician determines the flow rate, duration of use, method of administration, and oxygen source according to individual patient needs. Two landmark randomized controlled trials (RCTs) of patients with COPD established the role of LTOT in COPD. Questions regarding the use of LTOT, however, still remain.
Research Question
What is the effectiveness, cost-effectiveness, and safety of LTOT compared with no LTOT in patients with COPD, who are stratified by severity of hypoxemia?
Research Methods
Literature Search
Search Strategy
A literature search was performed on September 8, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Library, and INAHTA for studies published from January 1, 2007 to September 8, 2010.
A single clinical epidemiologist reviewed the abstracts, obtained full-text articles for studies meeting the eligibility criteria, and examined reference lists for additional relevant studies not identified through the literature search. A second clinical epidemiologist and then a group of epidemiologists reviewed articles with an unknown eligibility until consensus was established.
Inclusion Criteria
patients with mild, moderate, or severe hypoxemia;
English-language articles published between January 1, 2007 and September 8, 2010;
journal articles reporting on effectiveness, cost-effectiveness, or safety for the comparison of interest;
clearly described study design and methods;
health technology assessments, systematic reviews, RCTs, or prospective cohort observational studies;
any type of observational study for the evaluation of safety.
Exclusion Criteria
no hypoxemia
non-English papers
animal or in vitro studies
case reports, case series, or case-case studies
studies comparing different oxygen therapy regimens
studies on nocturnal oxygen therapy
studies on short-burst, palliative, or ambulatory oxygen (supplemental oxygen during exercise or activities of daily living)
Outcomes of Interest
mortality/survival
hospitalizations
readmissions
forced expiratory volume in 1 second (FEV1)
forced vital capacity (FVC)
FEV1/FVC
pulmonary hypertension
arterial partial pressure of oxygen (PaO2)
arterial partial pressure of carbon dioxide (PaCO2)
end-exercise dyspnea score
endurance time
health-related quality of life
Note: Outcomes of interest were formulated according to existing studies, with arterial pressure of oxygen and carbon dioxide as surrogate outcomes.
Summary of Findings
Conclusions
Based on low quality of evidence, LTOT (~ 15 hours/day) decreases all-cause mortality in patients with COPD who have severe hypoxemia (PaO2 ~ 50 mm Hg) and heart failure.
The effect for all-cause mortality had borderline statistical significance when the control group was no LTOT: one study.
Based on low quality of evidence, there is no beneficial effect of LTOT on all-cause mortality at 3 and 7 years in patients with COPD who have mild-to-moderate hypoxemia (PaO2 ~ 59-65 mm Hg)1
Based on very low quality of evidence, there is some suggestion that LTOT may have a beneficial effect over time on FEV1 and PaCO2 in patients with COPD who have severe hypoxemia and heart failure: improved methods are needed.
Based on very low quality of evidence, there is no beneficial effect of LTOT on lung function or exercise factors in patients with COPD who have mild-to-moderate hypoxemia, whether survivors or nonsurvivors are assessed.
Based on low to very low quality of evidence, LTOT does not prevent readmissions in patients with COPD who have severe hypoxemia. Limited data suggest LTOT increases the risk of hospitalizations.
Limited work has been performed evaluating the safety of LTOT by severity of hypoxemia.
Based on low to very low quality of evidence, LTOT may have a beneficial effect over time on health-related quality of life in patients with COPD who have severe hypoxemia. Limited work using disease-specific instruments has been performed.
Ethical constraints of not providing LTOT to eligible patients with COPD prohibit future studies from examining LTOT outcomes in an ideal way.
PMCID: PMC3384376  PMID: 23074435
6.  Pulmonary Rehabilitation for Patients With Chronic Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based review was to determine the effectiveness and cost-effectiveness of pulmonary rehabilitation in the management of chronic obstructive pulmonary disease (COPD).
Technology
Pulmonary rehabilitation refers to a multidisciplinary program of care for patients with chronic respiratory impairment that is individually tailored and designed to optimize physical and social performance and autonomy. Exercise training is the cornerstone of pulmonary rehabilitation programs, though they may also include components such as patient education and psychological support. Pulmonary rehabilitation is recommended as the standard of care in the treatment and rehabilitation of patients with COPD who remain symptomatic despite treatment with bronchodilators.
For the purpose of this review, the Medical Advisory Secretariat focused on pulmonary rehabilitation programs as defined by the Cochrane Collaboration—that is, any inpatient, outpatient, or home-based rehabilitation program lasting at least 4 weeks that includes exercise therapy with or without any form of education and/or psychological support delivered to patients with exercise limitations attributable to COPD.
Research Questions
What is the effectiveness and cost-effectiveness of pulmonary rehabilitation compared with usual care (UC) for patients with stable COPD?
Does early pulmonary rehabilitation (within 1 month of hospital discharge) in patients who had an acute exacerbation of COPD improve outcomes compared with UC (or no rehabilitation)?
Do maintenance or postrehabilitation programs for patients with COPD who have completed a pulmonary rehabilitation program improve outcomes compared with UC?
Research Methods
Literature Search
Search Strategy
For Research Questions 1and 2, a literature search was performed on August 10, 2010 for studies published from January 1, 2004 to July 31, 2010. For Research Question 3, a literature search was performed on February 3, 2011 for studies published from January 1, 2000 to February 3, 2011. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists and health technology assessment websites were also examined for any additional relevant studies not identified through the systematic search.
Inclusion Criteria
Research questions 1 and 2:
published between January 1, 2004 and July 31, 2010
randomized controlled trials, systematic reviews, and meta-analyses
COPD study population
studies comparing pulmonary rehabilitation with UC (no pulmonary rehabilitation)
duration of pulmonary rehabilitation program ≥ 6 weeks
pulmonary rehabilitation program had to include at minimum exercise training
Research question 3:
published between January 1, 2000 and February 3, 2011
randomized controlled trials, systematic reviews, and meta-analyses
COPD study population
studies comparing a maintenance or postrehabilitation program with UC (standard follow-up)
duration of pulmonary rehabilitation program ≥ 6 weeks
initial pulmonary rehabilitation program had to include at minimum exercise training
Exclusion Criteria
Research questions 1, 2, and 3:
grey literature
duplicate publications
non-English language publications
study population ≤ 18 years of age
studies conducted in a palliative population
studies that did not report primary outcome of interest
Additional exclusion criteria for research question 3:
studies with ≤ 2 sessions/visits per month
Outcomes of Interest
The primary outcomes of interest for the stable COPD population were exercise capacity and health-related quality of life (HRQOL). For the COPD population following an exacerbation, the primary outcomes of interest were hospital readmissions and HRQOL. The primary outcomes of interest for the COPD population undertaking maintenance programs were functional exercise capacity and HRQOL.
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Research Question 1: Effect of Pulmonary Rehabilitation on Outcomes in Stable COPD
Seventeen randomized controlled trials met the inclusion criteria and were included in this review.
The following conclusions are based on moderate quality of evidence.
Pulmonary rehabilitation including at least 4 weeks of exercise training leads to clinically and statistically significant improvements in HRQOL in patients with COPD.1
Pulmonary rehabilitation also leads to a clinically and statistically significant improvement in functional exercise capacity2 (weighted mean difference, 54.83 m; 95% confidence interval, 35.63–74.03; P < 0.001).
Research Question 2: Effect of Pulmonary Rehabilitation on Outcomes Following an Acute Exacerbation of COPD
Five randomized controlled trials met the inclusion criteria and are included in this review. The following conclusion is based on moderate quality of evidence.
Pulmonary rehabilitation (within 1 month of hospital discharge) after acute exacerbation significantly reduces hospital readmissions (relative risk, 0.50; 95% confidence interval, 0.33–0.77; P = 0.001) and leads to a statistically and clinically significant improvement in HRQOL.3
Research Question 3: Effect of Pulmonary Rehabilitation Maintenance Programs on COPD Outcomes
Three randomized controlled trials met the inclusion criteria and are included in this review. The conclusions are based on a low quality of evidence and must therefore be considered with caution.
Maintenance programs have a nonsignificant effect on HRQOL and hospitalizations.
Maintenance programs have a statistically but not clinically significant effect on exercise capacity (P = 0.01). When subgrouped by intensity and quality of study, maintenance programs have a statistically and marginally clinically significant effect on exercise capacity.
PMCID: PMC3384375  PMID: 23074434
7.  Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease 
Thorax  2007;62(11):932-937.
Background
Airflow limitation in chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from the classic phenotypes of “pink puffers” and “blue bloaters”.
Methods
To characterise clinical phenotypes based on severity of emphysema, 274 subjects with COPD were recruited, excluding those with physician‐diagnosed bronchial asthma. For all subjects a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg) and high‐resolution CT scanning were performed.
Results
Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema had significantly lower body mass index (BMI) and poorer QOL scores, evaluated using St George's Respiratory Questionnaire (SGRQ), than those with no/mild emphysema (mean (SD) BMI 21.2 (0.5) vs 23.5 (0.3) kg/m2, respectively; SGRQ total score 40 (3) vs 28 (2), respectively; p<0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen.
Conclusions
The severity of emphysema varies widely even in patients with the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. Patients with the phenotype in which emphysema predominates have lower BMI and poorer health‐related QOL.
doi:10.1136/thx.2006.072777
PMCID: PMC2117136  PMID: 17573447
8.  Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease (COPD) Using an Ontario Policy Model 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Background
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The inflammation causes repeated cycles of injury and repair in the airway wall— inflammatory cells release a variety of chemicals and lead to cellular damage. The inflammation process also contributes to the loss of elastic recoil pressure in the lung, thereby reducing the driving pressure for expiratory flow through narrowed and poorly supported airways, in which airflow resistance is significantly increased. Expiratory flow limitation is the pathophysiological hallmark of COPD.
Exacerbations of COPD contribute considerably to morbidity and mortality, and impose a burden on the health care system. They are a leading cause of emergency room visits and hospitalizations, particularly in the winter. In Canada, the reported average cost for treating a moderate exacerbation is $641; for a major exacerbation, the cost is $10,086.
Objective
The objective of this study was to evaluate the cost-effectiveness and budget impact of the following interventions in moderate to very severe COPD, investigated in the Medical Advisory Secretariat Chronic Obstructive Pulmonary Disease Mega-Analysis Series:
smoking cessation programs in moderate COPD in an outpatient setting:
– intensive counselling (IC) versus usual care (UC)
– nicotine replacement therapy (NRT) versus UC
– IC + NRT versus placebo
– bupropion versus placebo
multidisciplinary care (MDC) teams versus UC in moderate to severe COPD in an outpatient setting
pulmonary rehabilitation (PR) versus UC following acute exacerbations in moderate to severe COPD
long-term oxygen therapy (LTOT) versus UC in severe hypoxemia in COPD in an outpatient setting
ventilation:
– noninvasive positive pressure ventilation (NPPV) + usual medical care versus usual medical care in acute respiratory failure due to an acute exacerbation in severe COPD in an inpatient setting
– weaning with NPPV versus weaning with invasive mechanical ventilation in acute respiratory failure due to an acute exacerbation in very severe COPD in an inpatient setting
Methods
A cost-utility analysis was conducted using a Markov probabilistic model. The model consists of different health states based on the Global Initiative for Chronic Obstructive Lung Disease COPD severity classification. Patients were assigned different costs and utilities depending on their severity health state during each model cycle. In addition to moving between health states, patients were at risk of acute exacerbations of COPD in each model cycle. During each cycle, patients could have no acute exacerbation, a minor acute exacerbation, or a major exacerbation. For the purposes of the model, a major exacerbation was defined as one that required hospitalization. Patients were assigned different costs and utilities in each model cycle, depending on whether they experienced an exacerbation, and its severity.
Starting cohorts reflected the various patient populations from the trials analyzed. Incremental cost-effectiveness ratios (ICERs)—that is, costs per quality-adjusted life-year (QALY)—were estimated for each intervention using clinical parameters and summary estimates of relative risks of (re)hospitalization, as well as mortality and abstinence rates, from the COPD mega-analysis evidence-based analyses.
A budget impact analysis was also conducted to project incremental costs already being incurred or resources already in use in Ontario. Using provincial data, medical literature, and expert opinion, health system impacts were calculated for the strategies investigated.
All costs are reported in Canadian dollars.
Results
All smoking cessation programs were dominant (i.e., less expensive and more effective overall). Assuming a base case cost of $1,041 and $1,527 per patient for MDC and PR, the ICER was calculated to be $14,123 per QALY and $17,938 per QALY, respectively. When the costs of MDC and PR were varied in a 1-way sensitivity analysis to reflect variation in resource utilization reported in the literature, the ICER increased to $55,322 per QALY and $56,270 per QALY, respectively. Assuming a base case cost of $2,261 per year per patient for LTOT as reported by data from the Ontario provincial program, the ICER was calculated to be $38,993 per QALY. Ventilation strategies were dominant (i.e., cheaper and more effective), as reflected by the clinical evidence of significant in-hospital days avoided in the study group.
Ontario currently pays for IC through physician billing (translating to a current burden of $8 million) and bupropion through the Ontario Drug Benefit program (translating to a current burden of almost $2 million). The burden of NRT was projected to be $10 million, with future expenditures of up to $1 million in Years 1 to 3 for incident cases.
Ontario currently pays for some chronic disease management programs. Based on the most recent Family Health Team data, the costs of MDC programs to manage COPD were estimated at $85 million in fiscal year 2010, with projected future expenditures of up to $51 million for incident cases, assuming the base case cost of the program. However, this estimate does not accurately reflect the current costs to the province because of lack of report by Family Health Teams, lack of capture of programs outside this model of care by any data set in the province, and because the resource utilization and frequency of visits/follow-up phone calls were based on the findings in the literature rather than the actual Family Health Team COPD management programs in place in Ontario. Therefore, MDC resources being utilized in the province are unknown and difficult to measure.
Data on COPD-related hospitalizations were pulled from Ontario administrative data sets and based on consultation with experts. Half of hospitalized patients will access PR resources at least once, and half of these will repeat the therapy, translating to a potential burden of $17 million to $32 million, depending on the cost of the program. These resources are currently being absorbed, but since utilization is not being captured by any data set in the province, it is difficult to quantify and estimate. Provincial programs may be under-resourced, and patients may not be accessing these services effectively.
Data from the LTOT provincial program (based on fiscal year 2006 information) suggested that the burden was $65 million, with potential expenditures of up to $0.2 million in Years 1 to 3 for incident cases.
From the clinical evidence on ventilation (i.e., reduction in length of stay in hospital), there were potential cost savings to the hospitals of $42 million and $12 million for NPPV and weaning with NPPV, respectively, if the study intervention were adopted. Future cost savings were projected to be up to $4 million and $1 million, respectively, for incident cases.
Conclusions
Currently, costs for most of these interventions are being absorbed by provider services, the Ontario Drug Benefit Program, the Assistive Devices Program, and the hospital global budget. The most cost-effective intervention for COPD will depend on decision-makers’ willingness to pay. Lack of provincial data sets capturing resource utilization for the various interventions poses a challenge for estimating current burden and future expenditures.
PMCID: PMC3384363  PMID: 23074422
9.  Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of multidisciplinary care (MDC) compared with usual care (UC, single health care provider) for the treatment of stable chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Chronic obstructive pulmonary disease is a progressive disorder with episodes of acute exacerbations associated with significant morbidity and mortality. Cigarette smoking is linked causally to COPD in more than 80% of cases. Chronic obstructive pulmonary disease is among the most common chronic diseases worldwide and has an enormous impact on individuals, families, and societies through reduced quality of life and increased health resource utilization and mortality.
The estimated prevalence of COPD in Ontario in 2007 was 708,743 persons.
Technology
Multidisciplinary care involves professionals from a range of disciplines, working together to deliver comprehensive care that addresses as many of the patient’s health care and psychosocial needs as possible.
Two variables are inherent in the concept of a multidisciplinary team: i) the multidisciplinary components such as an enriched knowledge base and a range of clinical skills and experiences, and ii) the team components, which include but are not limited to, communication and support measures. However, the most effective number of team members and which disciplines should comprise the team for optimal effect is not yet known.
Research Question
What is the effectiveness and cost-effectiveness of MDC compared with UC (single health care provider) for the treatment of stable COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on July 19, 2010 using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 1995 until July 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.
Inclusion Criteria
health technology assessments, systematic reviews, or randomized controlled trials
studies published between January 1995 and July 2010;
COPD study population
studies comparing MDC (2 or more health care disciplines participating in care) compared with UC (single health care provider)
Exclusion Criteria
grey literature
duplicate publications
non-English language publications
study population less than 18 years of age
Outcomes of Interest
hospital admissions
emergency department (ED) visits
mortality
health-related quality of life
lung function
Quality of Evidence
The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six randomized controlled trials were obtained from the literature search. Four of the 6 studies were completed in the United States. The sample size of the 6 studies ranged from 40 to 743 participants, with a mean study sample between 66 and 71 years of age. Only 2 studies characterized the study sample in terms of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria, and in general the description of the study population in the other 4 studies was limited. The mean percent predicted forced expiratory volume in 1 second (% predicted FEV1) among study populations was between 32% and 59%. Using this criterion, 3 studies included persons with severe COPD and 2 with moderate COPD. Information was not available to classify the population in the sixth study.
Four studies had MDC treatment groups which included a physician. All studies except 1 reported a respiratory specialist (i.e., respiratory therapist, specialist nurse, or physician) as part of the multidisciplinary team. The UC group was comprised of a single health care practitioner who may or may not have been a respiratory specialist.
A meta-analysis was completed for 5 of the 7 outcome measures of interest including:
health-related quality of life,
lung function,
all-cause hospitalization,
COPD-specific hospitalization, and
mortality.
There was only 1 study contributing to the outcome of all-cause and COPD-specific ED visits which precluded pooling data for these outcomes. Subgroup analyses were not completed either because heterogeneity was not significant or there were a small number of studies that were meta-analysed for the outcome.
Quality of Life
Three studies reported results of quality of life assessment based on the St. George’s Respiratory Questionnaire (SGRQ). A mean decrease in the SGRQ indicates an improvement in quality of life while a mean increase indicates deterioration in quality of life. In all studies the mean change score from baseline to the end time point in the MDC treatment group showed either an improvement compared with the control group or less deterioration compared with the control group. The mean difference in change scores between MDC and UC groups was statistically significant in all 3 studies. The pooled weighted mean difference in total SGRQ score was −4.05 (95% confidence interval [CI], −6.47 to 1.63; P = 0.001). The GRADE quality of evidence was assessed as low for this outcome.
Lung Function
Two studies reported results of the FEV1 % predicted as a measure of lung function. A negative change from baseline infers deterioration in lung function and a positive change from baseline infers an improvement in lung function. The MDC group showed a statistically significant improvement in lung function up to 12 months compared with the UC group (P = 0.01). However this effect is not maintained at 2-year follow-up (P = 0.24). The pooled weighted mean difference in FEV1 percent predicted was 2.78 (95% CI, −1.82 to −7.37). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
Hospital Admissions
All-Cause
Four studies reported results of all-cause hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 4 studies were pooled to determine a summary estimate. There is a statistically significant 25% relative risk (RR) reduction in all-cause hospitalizations in the MDC group compared with the UC group (P < 0.001). The index of heterogeneity (I2) value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
COPD-Specific Hospitalization
Three studies reported results of COPD-specific hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically significant 33% RR reduction in all-cause hospitalizations in the MDC group compared with the UC group (P = 0.002). The I2 value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
Emergency Department Visits
All-Cause
Two studies reported results of all-cause ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically nonsignificant reduction in all-cause ED visits when data from these 2 studies are pooled (RR, 0.64; 95% CI, 0.31 to −1.33; P = 0.24). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
COPD-Specific
One study reported results of COPD-specific ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically significant 41% reduction in COPD-specific ED visits when the data from these 2 studies are pooled (RR, 0.59; 95% CI, 0.43−0.81; P < 0.001). The GRADE quality of evidence was assessed as moderate for this outcome.
Mortality
Three studies reported the mortality during the study follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically nonsignificant reduction in mortality between treatment groups (RR, 0.81; 95% CI, 0.52−1.27; P = 0.36). The I2 value is 19%, indicating low statistical heterogeneity between studies. All studies had a 12-month follow-up period. The GRADE quality of evidence was assessed as low for this outcome.
Conclusions
Significant effect estimates with moderate quality of evidence were found for all-cause hospitalization, COPD-specific hospitalization, and COPD-specific ED visits (Table ES1). A significant estimate with low quality evidence was found for the outcome of quality of life (Table ES2). All other outcome measures were nonsignificant and supported by low or very low quality of evidence.
Summary of Dichotomous Data
Abbreviations: CI, confidence intervals; COPD, chronic obstructive pulmonary disease; n, number.
Summary of Continuous Data
Abbreviations: CI, confidence intervals; FEV1, forced expiratory volume in 1 second; n, number; SGRQ, St. George’s Respiratory Questionnaire.
PMCID: PMC3384374  PMID: 23074433
10.  Leptin Levels in Various Manifestations of Pulmonary Tuberculosis 
Mediators of Inflammation  2007;2007:64859.
Background. Proinflammatory cytokines are prime candidates as causative agents of the metabolic changes that eventually result in tuberculosis-associated weight loss. Microbial products and cytokines such as TNF and IL-1 increase leptin expression dose dependently in adipose tissue. Leptin plays an important role in cellular immunity. Objectives. In this study, we investigated serum leptin and TNF-α levels before and after antituberculosis therapy in patients with active pulmonary tuberculosis (TB). Methods. Twenty five in patients with active pulmonary TB and 18 healthy controls participated in the study. Leptin and TNF-α levels were measured before treatment and six months after the treatment and they were compared with the control group. Body mass index (BMI) and chest X-rays before and after the treatment were also evaluated. Results. The leptin levels before and after the treatment were 1.66±1.68 ng/mL and 3.26±3.81 ng/mL, respectively. The leptin levels of tuberculous patients were significant than in healthy patients (P < .05). The BMI was 19.36 ± 2.55 kg/m2 before the treatment and 22.87 ± 3.13 kg/m2 after the treatment. The TNF-α level was 23.19±12.78 pg/mL before the treatment and 15.95±6.58 pg/mL after the treatment. There was no correlation between leptin and TNF-α levels. Leptin levels were low in patients who had sequela lesion on chest radiographs. Conclusion. Leptin levels are suppressed in tuberculous patients and low leptin levels may contribute to increased susceptibility to infection and recovery with sequela lesions.
doi:10.1155/2007/64859
PMCID: PMC1804295  PMID: 17497033
11.  Lung Function and Incidence of Chronic Obstructive Pulmonary Disease after Improved Cooking Fuels and Kitchen Ventilation: A 9-Year Prospective Cohort Study 
PLoS Medicine  2014;11(3):e1001621.
Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China.
Please see later in the article for the Editors' Summary
Background
Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.
Methods and Findings
A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.
Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.
Conclusions
Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.
Trial Registration
Chinese Clinical Trial Register ChiCTR-OCH-12002398
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Nearly 3 billion people in developing countries heat their homes and cook by burning biomass—wood, crop waste, and animal dung—in open fires and leaky stoves. Burning biomass this way releases pollutants into the home that impair lung function and that are responsible for more than a million deaths from chronic obstructive pulmonary disease (COPD) every year. COPD is a group of diseases that interfere with breathing. Normally, air is breathed in through the nose or mouth and travels down the windpipe into two bronchial tubes (airways) in the lungs. These tubes branch into smaller tubes (bronchioles) that end in bunches of tiny air sacs (alveoli). Oxygen in the air passes through the thin walls of these sacs into small blood vessels and is taken to the heart for circulation round the body. The two main types of COPD—chronic bronchitis (long-term irritation and swelling of the bronchial tubes) and emphysema (damage to the walls of the alveoli)—make it hard for people to breathe. Most people with COPD have both chronic bronchitis and emphysema, both of which are caused by long-term exposure to cigarette smoke, indoor air pollution, and other lung irritants. Symptoms of COPD include breathlessness during exercise and a persistent cough that produces large amounts of phlegm (mucus). There is no cure for COPD, but drugs and oxygen therapy can relieve its symptoms, and avoiding lung irritants can slow disease progression.
Why Was This Study Done?
Exposure to indoor air pollution has been associated with impaired lung function and COPD in several studies. However, few studies have assessed the long-term effects on lung function and on the incidence of COPD (the proportion of a population that develops COPD each year) of replacing biomass with biogas (a clean fuel produced by bacterial digestion of biodegradable materials) for cooking and heating, or of improving kitchen ventilation during cooking. Here, the researchers undertook a nine-year prospective cohort study in rural southern China to investigate whether these interventions are associated with any effects on lung function and on the incidence of COPD. A prospective cohort study enrolls a group of people, determines their characteristics at baseline, and follows them over time to see whether specific characteristic are associated with specific outcomes.
What Did the Researchers Do and Find?
The researchers offered nearly 1,000 people living in 12 villages in southern China access to biogas and to improved kitchen ventilation. All the participants, who adopted these interventions according to personal preferences, completed a questionnaire about their smoking habits and occupational exposure to pollutants and had their lung function measured using a spirometry test at the start and end of the study. Some participants also completed a questionnaire and had their lung function measured three and six years into the study. Finally, the researchers measured levels of indoor air pollution in a randomly selected subset of homes at the end of the study to confirm that the interventions had reduced indoor air pollution. Compared with non-use, the use of clean fuels and of improved ventilation were both associated with a reduction in the decline in lung function over time after adjusting for known characteristics that affect lung function, such as smoking. The use of both interventions reduced the decline in lung function more markedly than either intervention alone, and the benefits of using the interventions increased with length of use. Notably, the combined use of both interventions reduced the risk of COPD occurrence among the study participants.
What Do These Findings Mean?
These findings suggest that, among people living in rural southern China, the combined interventions of use of biogas instead of biomass and improved kitchen ventilation were associated with a reduced decline in lung function over time and with a reduced risk of COPD. Because participants were not randomly allocated to intervention groups, the people who adopted the interventions may have shared other unknown characteristics (confounders) that affected their lung function (for example, having a healthier lifestyle). Thus, it is not possible to conclude that either intervention actually caused a reduction in the decline in lung function. Nevertheless, these findings suggest that the use of biogas as a substitute for biomass for cooking and heating and improvements in kitchen ventilation might lead to a reduction in the global burden of COPD associated with biomass smoke.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001621.
The US National Heart, Lung, and Blood Institute provides detailed information for the public about COPD
The US Centers for Disease Control and Prevention provides information about COPD and links to other resources (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about COPD, personal stories, and links to other resources
The British Lung Foundation, a not-for-profit organization, provides information about COPD in several languages
The Global Initiative for Chronic Obstructive Lung Disease works to improve prevention and treatment of COPD around the world
The World Health Organization provides information about all aspects of indoor air pollution and health (in English, French, and Spanish)
MedlinePlus provides links to other information about COPD (in English and Spanish)
doi:10.1371/journal.pmed.1001621
PMCID: PMC3965383  PMID: 24667834
12.  Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression. 
Journal of Clinical Investigation  1997;99(10):2398-2404.
The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.
PMCID: PMC508079  PMID: 9153282
13.  Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of smoking cessation interventions in the management of chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Tobacco smoking is the main risk factor for COPD. It is estimated that 50% of older smokers develop COPD and more than 80% of COPD-associated morbidity is attributed to tobacco smoking. According to the Canadian Community Health Survey, 38.5% of Ontarians who smoke have COPD. In patients with a significant history of smoking, COPD is usually present with symptoms of progressive dyspnea (shortness of breath), cough, and sputum production. Patients with COPD who smoke have a particularly high level of nicotine dependence, and about 30.4% to 43% of patients with moderate to severe COPD continue to smoke. Despite the severe symptoms that COPD patients suffer, the majority of patients with COPD are unable to quit smoking on their own; each year only about 1% of smokers succeed in quitting on their own initiative.
Technology
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. Smoking cessation can help to slow or halt the progression of COPD. Smoking cessation programs mainly target tobacco smoking, but may also encompass other substances that can be difficult to stop smoking due to the development of strong physical addictions or psychological dependencies resulting from their habitual use.
Smoking cessation strategies include both pharmacological and nonpharmacological (behavioural or psychosocial) approaches. The basic components of smoking cessation interventions include simple advice, written self-help materials, individual and group behavioural support, telephone quit lines, nicotine replacement therapy (NRT), and antidepressants. As nicotine addiction is a chronic, relapsing condition that usually requires several attempts to overcome, cessation support is often tailored to individual needs, while recognizing that in general, the more intensive the support, the greater the chance of success. Success at quitting smoking decreases in relation to:
a lack of motivation to quit,
a history of smoking more than a pack of cigarettes a day for more than 10 years,
a lack of social support, such as from family and friends, and
the presence of mental health disorders (such as depression).
Research Question
What are the effectiveness and cost-effectiveness of smoking cessation interventions compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on June 24, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations (1950 to June Week 3 2010), EMBASE (1980 to 2010 Week 24), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination for studies published between 1950 and June 2010. A single reviewer reviewed the abstracts and obtained full-text articles for those studies meeting the eligibility criteria. Reference lists were also examined for any additional relevant studies not identified through the search. Data were extracted using a standardized data abstraction form.
Inclusion Criteria
English-language, full reports from 1950 to week 3 of June, 2010;
either randomized controlled trials (RCTs), systematic reviews and meta-analyses, or non-RCTs with controls;
a proven diagnosis of COPD;
adult patients (≥ 18 years);
a smoking cessation intervention that comprised at least one of the treatment arms;
≥ 6 months’ abstinence as an outcome; and
patients followed for ≥ 6 months.
Exclusion Criteria
case reports
case series
Outcomes of Interest
≥ 6 months’ abstinence
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Nine RCTs were identified from the literature search. The sample sizes ranged from 74 to 5,887 participants. A total of 8,291 participants were included in the nine studies. The mean age of the patients in the studies ranged from 54 to 64 years. The majority of studies used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD staging criteria to stage the disease in study subjects. Studies included patients with mild COPD (2 studies), mild-moderate COPD (3 studies), moderate–severe COPD (1 study) and severe–very severe COPD (1 study). One study included persons at risk of COPD in addition to those with mild, moderate, or severe COPD, and 1 study did not define the stages of COPD. The individual quality of the studies was high. Smoking cessation interventions varied across studies and included counselling or pharmacotherapy or a combination of both. Two studies were delivered in a hospital setting, whereas the remaining 7 studies were delivered in an outpatient setting. All studies reported a usual care group or a placebo-controlled group (for the drug-only trials). The follow-up periods ranged from 6 months to 5 years. Due to excessive clinical heterogeneity in the interventions, studies were first grouped into categories of similar interventions; statistical pooling was subsequently performed, where appropriate. When possible, pooled estimates using relative risks for abstinence rates with 95% confidence intervals were calculated. The remaining studies were reported separately.
Abstinence Rates
Table ES1 provides a summary of the pooled estimates for abstinence, at longest follow-up, from the trials included in this review. It also shows the respective GRADE qualities of evidence.
Summary of Results*
Abbreviations: CI, confidence interval; NRT, nicotine replacement therapy.
Statistically significant (P < 0.05).
One trial used in this comparison had 2 treatment arms each examining a different antidepressant.
Conclusions
Based on a moderate quality of evidence, compared with usual care, abstinence rates are significantly higher in COPD patients receiving intensive counselling or a combination of intensive counselling and NRT.
Based on limited and moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving NRT compared with placebo.
Based on a moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving the antidepressant bupropion compared to placebo.
PMCID: PMC3384371  PMID: 23074432
14.  Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this health technology assessment was to determine the effectiveness and cost-effectiveness of noninvasive ventilation for stable chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Noninvasive ventilation is used for COPD patients with chronic respiratory failure. Chronic respiratory failure in COPD patients may be due to the inability of the pulmonary system to coordinate ventilation, leading to adverse arterial levels of oxygen and carbon dioxide. Noninvasive ventilation in stable COPD patients has the potential to improve quality of life, prolong survival, and improve gas exchange and sleep quality in patients who are symptomatic after optimal therapy, have hypercapnia or nocturnal hypoventilation and mild hypercapnia, and are frequently hospitalized.
Technology
Noninvasive positive pressure ventilation (NPPV) is any form of positive ventilatory support without the use of an endotracheal tube. For stable COPD, the standard of care when using noninvasive ventilation is bilevel positive airway pressure (BiPAP). Bilevel positive airway pressure involves both inspiratory and expiratory pressure, high during inspiration and lower during expiration. It acts as a pressure support to accentuate a patient’s inspiratory efforts. The gradient between pressures maintains alveolar ventilation and helps to reduce carbon dioxide levels. Outpatients typically use BiPAP at night. Additional advantages of using BiPAP include resting of respiratory muscles, decreased work of breathing, and control of obstructive hypopnea.
Research Question
What is the effectiveness and cost-effectiveness of noninvasive ventilation, compared with no ventilation while receiving usual care, for stable COPD patients?
Research Methods
Literature Search
Search Strategy
A literature search was performed on December 3, 2010, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published from January 1, 2004 to December 3, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. When the reviewer was unsure of the eligibility of articles, a second clinical epidemiologist and then a group of epidemiologists reviewed these until consensus was reached.
Inclusion Criteria
full-text English language articles,
studies published between January 1, 2004 and December 3, 2010,
journal articles that report on the effectiveness or cost-effectiveness of noninvasive ventilation,
clearly described study design and methods, and
health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs).
Exclusion Criteria
non-English papers
animal or in vitro studies
case reports, case series, or case-case studies
cross-over RCTs
studies on noninvasive negative pressure ventilation (e.g., iron lung)
studies that combine ventilation therapy with other regimens (e.g., daytime NPPV plus exercise or pulmonary rehabilitation)
studies on heliox with NPPV
studies on pulmonary rehabilitation with NPPV
Outcomes of Interest
mortality/survival
hospitalizations/readmissions
length of stay in hospital
forced expiratory volume
arterial partial pressure of oxygen
arterial partial pressure of carbon dioxide
dyspnea
exercise tolerance
health-related quality of life
Note: arterial pressure of oxygen and carbon dioxide are surrogate outcomes.
Statistical Methods
A meta-analysis and an analysis of individual studies were performed using Review Manager Version 5. For continuous data, a mean difference was calculated, and for dichotomous data, a relative risk ratio was calculated for RCTs. For continuous variables with mean baseline and mean follow-up data, a change value was calculated as the difference between the 2 mean values.
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Conclusions
The following conclusions refer to stable, severe COPD patients receiving usual care.
Short-Term Studies
Based on low quality of evidence, there is a beneficial effect of NPPV compared with no ventilation on oxygen gas exchange, carbon dioxide gas exchange, and exercise tolerance measured using the 6 Minute Walking Test.
Based on very low quality of evidence, there is no effect of NPPV therapy on lung function measured as forced expiratory volume in 1 second (Type II error not excluded).
Long-Term Studies
Based on moderate quality of evidence, there is no effect of NPPV therapy for the outcomes of mortality, lung function measured as forced expiratory volume in 1 second, and exercise tolerance measured using the 6 Minute Walking Test.
Based on low quality of evidence, there is no effect of NPPV therapy for the outcomes of oxygen gas exchange and carbon dioxide gas exchange (Type II error not excluded).
Qualitative Assessment
Based on low quality of evidence, there is a beneficial effect of NPPV compared with no ventilation for dyspnea based on reduced Borg score or Medical Research Council dyspnea score.
Based on moderate quality of evidence, there is no effect of NPPV therapy for hospitalizations.
Health-related quality of life could not be evaluated.
PMCID: PMC3384378  PMID: 23074437
15.  Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection 
AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications.
METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically.
RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13±3.94), (5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C.
CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.
doi:10.3748/wjg.v11.i22.3357
PMCID: PMC4315988  PMID: 15948239
Chronic hepatitis C; Leptin; Anthropometric parameter; Lipid metabolism
16.  Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis 
Respiratory Research  2011;12(1):157.
Background
Osteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.
Methods
Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls.
Results
Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001). Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables. The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.
Conclusions
Radiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.
doi:10.1186/1465-9921-12-157
PMCID: PMC3260206  PMID: 22176920
chronic obstructive pulmonary disease; pulmonary emphysema; osteoporosis; cytokine; OPG/RANK/RANKL
17.  Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients with Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this analysis was to compare hospital-at-home care with inpatient hospital care for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) who present to the emergency department (ED).
Clinical Need: Condition and Target Population
Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease is a disease state characterized by airflow limitation that is not fully reversible. This airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The natural history of COPD involves periods of acute-onset worsening of symptoms, particularly increased breathlessness, cough, and/or sputum, that go beyond normal day-to-day variations; these are known as acute exacerbations.
Two-thirds of COPD exacerbations are caused by an infection of the tracheobronchial tree or by air pollution; the cause in the remaining cases is unknown. On average, patients with moderate to severe COPD experience 2 or 3 exacerbations each year.
Exacerbations have an important impact on patients and on the health care system. For the patient, exacerbations result in decreased quality of life, potentially permanent losses of lung function, and an increased risk of mortality. For the health care system, exacerbations of COPD are a leading cause of ED visits and hospitalizations, particularly in winter.
Technology
Hospital-at-home programs offer an alternative for patients who present to the ED with an exacerbation of COPD and require hospital admission for their treatment. Hospital-at-home programs provide patients with visits in their home by medical professionals (typically specialist nurses) who monitor the patients, alter patients’ treatment plans if needed, and in some programs, provide additional care such as pulmonary rehabilitation, patient and caregiver education, and smoking cessation counselling.
There are 2 types of hospital-at-home programs: admission avoidance and early discharge hospital-at-home. In the former, admission avoidance hospital-at-home, after patients are assessed in the ED, they are prescribed the necessary medications and additional care needed (e.g., oxygen therapy) and then sent home where they receive regular visits from a medical professional. In early discharge hospital-at-home, after being assessed in the ED, patients are admitted to the hospital where they receive the initial phase of their treatment. These patients are discharged into a hospital-at-home program before the exacerbation has resolved. In both cases, once the exacerbation has resolved, the patient is discharged from the hospital-at-home program and no longer receives visits in his/her home.
In the models that exist to date, hospital-at-home programs differ from other home care programs because they deal with higher acuity patients who require higher acuity care, and because hospitals retain the medical and legal responsibility for patients. Furthermore, patients requiring home care services may require such services for long periods of time or indefinitely, whereas patients in hospital-at-home programs require and receive the services for a short period of time only.
Hospital-at-home care is not appropriate for all patients with acute exacerbations of COPD. Ineligible patients include: those with mild exacerbations that can be managed without admission to hospital; those who require admission to hospital; and those who cannot be safely treated in a hospital-at-home program either for medical reasons and/or because of a lack of, or poor, social support at home.
The proposed possible benefits of hospital-at-home for treatment of exacerbations of COPD include: decreased utilization of health care resources by avoiding hospital admission and/or reducing length of stay in hospital; decreased costs; increased health-related quality of life for patients and caregivers when treated at home; and reduced risk of hospital-acquired infections in this susceptible patient population.
Ontario Context
No hospital-at-home programs for the treatment of acute exacerbations of COPD were identified in Ontario. Patients requiring acute care for their exacerbations are treated in hospitals.
Research Question
What is the effectiveness, cost-effectiveness, and safety of hospital-at-home care compared with inpatient hospital care of acute exacerbations of COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on August 5, 2010, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published from January 1, 1990, to August 5, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists and health technology assessment websites were also examined for any additional relevant studies not identified through the systematic search.
Inclusion Criteria
English language full-text reports;
health technology assessments, systematic reviews, meta-analyses, and randomized controlled trials (RCTs);
studies performed exclusively in patients with a diagnosis of COPD or studies including patients with COPD as well as patients with other conditions, if results are reported for COPD patients separately;
studies performed in patients with acute exacerbations of COPD who present to the ED;
studies published between January 1, 1990, and August 5, 2010;
studies comparing hospital-at-home and inpatient hospital care for patients with acute exacerbations of COPD;
studies that include at least 1 of the outcomes of interest (listed below).
Cochrane Collaboration reviews have defined hospital-at-home programs as those that provide patients with active treatment for their acute exacerbation in their home by medical professionals for a limited period of time (in this case, until the resolution of the exacerbation). If a hospital-at-home program had not been available, these patients would have been admitted to hospital for their treatment.
Exclusion Criteria
< 18 years of age
animal studies
duplicate publications
grey literature
Outcomes of Interest
Patient/clinical outcomes
mortality
lung function (forced expiratory volume in 1 second)
health-related quality of life
patient or caregiver preference
patient or caregiver satisfaction with care
complications
Health system outcomes
hospital readmissions
length of stay in hospital and hospital-at-home
ED visits
transfer to long-term care
days to readmission
eligibility for hospital-at-home
Statistical Methods
When possible, results were pooled using Review Manager 5 Version 5.1; otherwise, results were summarized descriptively. Data from RCTs were analyzed using intention-to-treat protocols. In addition, a sensitivity analysis was done assigning all missing data/withdrawals to the event. P values less than 0.05 were considered significant. A priori subgroup analyses were planned for the acuity of hospital-at-home program, type of hospital-at-home program (early discharge or admission avoidance), and severity of the patients’ COPD. Additional subgroup analyses were conducted as needed based on the identified literature. Post hoc sample size calculations were performed using STATA 10.1.
Quality of Evidence
The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Fourteen studies met the inclusion criteria and were included in this review: 1 health technology assessment, 5 systematic reviews, and 7 RCTs.
The following conclusions are based on low to very low quality of evidence. The reviewed evidence was based on RCTs that were inadequately powered to observe differences between hospital-at-home and inpatient hospital care for most outcomes, so there is a strong possibility of type II error. Given the low to very low quality of evidence, these conclusions must be considered with caution.
Approximately 21% to 37% of patients with acute exacerbations of COPD who present to the ED may be eligible for hospital-at-home care.
Of the patients who are eligible for care, some may refuse to participate in hospital-at-home care.
Eligibility for hospital-at-home care may be increased depending on the design of the hospital-at-home program, such as the size of the geographical service area for hospital-at-home and the hours of operation for patient assessment and entry into hospital-at-home.
Hospital-at-home care for acute exacerbations of COPD was associated with a nonsignificant reduction in the risk of mortality and hospital readmissions compared with inpatient hospital care during 2- to 6-month follow-up.
Limited, very low quality evidence suggests that hospital readmissions are delayed in patients who received hospital-at-home care compared with those who received inpatient hospital care (mean additional days before readmission comparing hospital-at-home to inpatient hospital care ranged from 4 to 38 days).
There is insufficient evidence to determine whether hospital-at-home care, compared with inpatient hospital care, is associated with improved lung function.
The majority of studies did not find significant differences between hospital-at-home and inpatient hospital care for a variety of health-related quality of life measures at follow-up. However, follow-up may have been too late to observe an impact of hospital-at-home care on quality of life.
A conclusion about the impact of hospital-at-home care on length of stay for the initial exacerbation (defined as days in hospital or days in hospital plus hospital-at-home care for inpatient hospital and hospital-at-home, respectively) could not be determined because of limited and inconsistent evidence.
Patient and caregiver satisfaction with care is high for both hospital-at-home and inpatient hospital care.
PMCID: PMC3384361  PMID: 23074420
18.  Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia 
Objective
In this study, we determined circulating levels of C-reactive protein, several cytokines, chemokines, adhesion molecules and angiogenic factors along with those of leptin in healthy non-pregnant and pregnant women and preeclamptic patients, and investigated whether serum leptin levels were related to the clinical characteristics and measured laboratory parameters of the study participants.
Methods
Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Levels of leptin and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum C-reactive protein (CRP) concentrations were measured by an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied.
Results
There were significant differences in most of the measured laboratory parameters among the three study groups except for serum IL-1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in preeclamptic patients and healthy pregnant women than in healthy non-pregnant women. Additionally, preeclamptic patients had significantly higher leptin levels as compared to healthy pregnant women. Serum leptin levels were independently associated with BMI in healthy non-pregnant women. In healthy pregnant women, both BMI and serum CRP concentrations showed significant positive linear association with leptin levels. There were significant positive correlations between serum leptin concentrations of healthy pregnant women and systolic blood pressure, as well as serum levels of IP-10, while their serum leptin levels correlated inversely with fetal birth weight. In preeclamptic patients, a significant positive correlation was observed between serum concentrations of leptin and IP-10. Furthermore, elevated serum leptin level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.
Conclusions
Simultaneous measurement of leptin with several inflammatory molecules and angiogenic factors in this study enabled us to investigate their relationship, which can help to understand the role of circulating leptin in normal pregnancy and preeclampsia.
doi:10.1186/1477-7827-9-124
PMCID: PMC3184629  PMID: 21906313
19.  The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease 
Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD). Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking. The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-α), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD. This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center. Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry. Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%). On bivariate analysis, there was no association between TNF-α and BMD. Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density. However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability. Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis. The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis. We conclude that the effect of adipokines on BMD does not appear to be independent of body mass. However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD.
PMCID: PMC2719257  PMID: 19657401
bone mineral density; osteoporosis; TNF-α; leptin; adiponectin; chronic obstructive pulmonary disease; adipokines
20.  The Role of Obesity, Different Fat Compartments and Sleep Apnea Severity in Circulating Leptin Levels: The Icelandic Sleep Apnea Cohort Study 
Objectives
To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between OSA severity and leptin levels differs depending on obesity level.
Methods
Cross-sectional study of 452 untreated obstructive sleep apnea (OSA) patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±SD), BMI 32.7±5.3 kg/m2 and apnea-hypopnea index (AHI) 40.2 ± 16.1 events/hour. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed as well as fasting serum morning leptin levels measured.
Results
Leptin levels were more highly correlated with body mass index (BMI), total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI<30, BMI 30–35 and BMI>35 kg/m2). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (p=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).
Conclusion
Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.
doi:10.1038/ijo.2012.138
PMCID: PMC3537909  PMID: 22964793
Obstructive sleep apnea; leptin; visceral fat; subcutaneous fat; obesity; hypertension
21.  A new inflammation marker of chronic obstructive pulmonary disease–adiponectin 
BACKGROUND:
This study was undertaken to measure the concentration of adiponectin (APN) in serum and induced sputum in patients with chronic obstructive pulmonary disease (COPD during acute exacerbation (AECOPD) and at stable stage and to determine the role of APN as a marker of inflammation in the pathogenesis of COPD.
METHODS:
All the patients in this prospective study were enrolled from October 2008 to October 2009, including 30 male AECOPD patients from the emergency department, 30 male stable COPD patients from the department of respiratory diseases, and 30 healthy non-smoking male controls from the department of medical examination. The serum and induced sputum were collected from each patient. All of the patients had normal weight (BMI range 18.5-24.9 kg/m2). Patients with severe bronchial asthma, bronchiectasis or autoimmune disease were excluded. Cell count and classification was performed for the induced sputum. The concentrations of APN, IL-8, IL-6 and TNF-α were measured by ELISA. Pulmonary function was tested among the three groups. Comparisons between the groups were conducted by Student’s t test, ANOVA analysis or nonparametric test. Correlation analysis was carried out by Pearson’s product-moment correlation coefficient test or Spearman’s rank-order correlation coefficient test.
RESULTS:
The concentrations of APN in the serum or induced sputum in AECOPD patients were significantly higher than those in stable COPD patients or healthy non-smoking controls (P<0.01). The concentration of APN in stable COPD patients was significantly higher than that in healthy non-smoking controls (P<0.01). For the AECOPD patients, APN was positively correlated with IL-8 and TNF-α in the serum and induced sputum (r=0.739, 0.734, 0.852, 0.857 respectively, P<0.05). For the stable COPD patients, APN was also positively correlated with IL-8 and TNF-α in the serum and induced sputum (r=0.751, 0.659, 0.707, 0.867 respectively, P<0.05). In addition, for the AECOPD patients, APN was positively correlated with the percentage of neutrophils in the induced sputum (r=0.439, P<0.05).
CONCLUSIONS:
APN is involved in the process of systematic and airway inflammation of COPD. This process is related to neutrophils in the airway, IL-8 and TNF-α. APN could be used as a new marker for inflammation of COPD.
PMCID: PMC4129679  PMID: 25214966
Chronic obstructive pulmonary disease; Serum; Induced sputum; Adiponectin; Neutrophil; Interleukin-8; Tumor necrosis factor-a; Interleukin-6
22.  Serum Leptin Concentrations in Human Immunodeficiency Virus–Infected Men With Low Adiposity 
The product of the obese gene (ob) is the protein leptin, which is synthesized in and secreted from adipocytes. Fasting serum leptin concentrations are closely related to body fat content and are higher in obese than in normal-weight individuals. Leptin may contribute to body weight regulation. Overproduction of leptin in certain pathologic conditions such as acquired immunodeficiency syndrome (AIDS) might in principle contribute to the low body fat content associated with body wasting. We measured fasting serum leptin levels by radioimmunoassay in individuals infected with the human immunodeficiency virus (HIV) and in a group of healthy lean men to determine whether HIV infection increases leptin levels. Thirteen HIV-infected men aged 26 to 50 years with a body mass index (BMI) of 15 to 26 kg/m2 and 4 to 24 kg body fat (7% to 29% body fat) had serum leptin levels (3.4 ± 1.6 ng/mL) that were not elevated compared with the levels in 17 healthy men (4.0 ± 1.4 ng/mL) matched for age (23 to 47 years), BMI (18 to 26 kg/m2), and body fat (5 to 21 kg; 9% to 28%). In both groups of men, serum leptin concentrations were correlated with percent body fat and body fat content (P < .001), and these relationships were not different between the two groups. In both groups, leptin concentrations were not correlated with lean body mass (P ≥ .24). Energy intake in the HIV-infected men, assessed from 3-day intake records, was within the normal range. These findings extend the hypothesis that circulating leptin concentrations directly reflect adipose tissue mass, even in HIV-infected men with low body fat content. These findings do not support the hypothesis that HIV infection is associated with high circulating leptin concentrations, and suggest that low leptin levels do not stimulate food intake in HIV-infected individuals.
PMCID: PMC3176667  PMID: 9054474
23.  Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients 
Background
Leptin is an hormone that regulates body weight. Studies have shown increasing leptin concentrations according to body mass index (BMI) and intermittent hypoxia.
Our aim is to evaluate the basal leptin levels in OSA patients and its possible relation to OSA severity, independently of confounders and investigate the Autoadjusting-CPAP effect on leptin values.
Methods
In ninety eight male patients with moderate to severe OSA leptin serum levels were evaluated before therapy, 9 days and 6 months after therapy.
Results
In this group mean age was 55.3 years, mean BMI was 33.2 Kg/m2 and mean Apnoea- Hypopnea Index (AHI) was 51.7/h. Mean basal serum leptin value was 12.1 ug/L. Univariate analysis showed a significant correlation between serum leptin values and BMI (R = 0.68; p < 0.001), waist-hip ratio (R = 0.283; p = 0.004) and AHI (R = 0.198; p = 0.048); in stepwise multiple regression analysis only BMI (p < 0.001) was a predictor of serum leptin values.
One week after therapy, mean leptin serum level decreased to 11.0 ug/L and 6 months after it was 11.4 ug/L. (p = 0.56 and p = 0.387, respectively)
Conclusion
Baseline leptin serum levels positively correlate with BMI, fat distributioand OSA severity.
BMI is the only predictor of basal leptin levels.
Treatment with Autoadjusting-CPAP has a small effect on leptin levels.
doi:10.1186/1471-2466-8-21
PMCID: PMC2567288  PMID: 18828917
24.  Body Composition in Patients with Chronic Obstructive Pulmonary Disease 
Mædica  2014;9(1):25-32.
Objectives:
Body composition assessment in chronic obstructive pulmonary disease (COPD) is important, as weight loss and muscular wasting are responsible for low exercise capacity in these patients, and low body mass index (BMI) and fat free mass index (FFMI) are important prognostic factors. Our study aims were: (a) to describe body composition in COPD patients referred to a pulmonary rehabilitation center in Bucharest; (b) to examine the relationships between body composition and disease severity (bronchial obstruction, exercise capacity, quality of life); (c) to test if segmental wasting of lower limbs muscle mass (measured by segmental body composition analysis) correlates with decreased exercise capacity.
Material and methods:
We studied 36 consecutive COPD patients referred to our clinic for pulmonary rehabilitation. Patients performed pulmonary function tests, six minutes walking test (6MWT), and health status was evaluated with COPD Assessment Test (CAT). Body composition measurements were performed by direct segmental multi-frequency bioelectrical impedance analysis (BIA).
Outcomes:
This study offers the first data on body composition of Romanian COPD patients
The prevalence of nutritional depletion (defined by low BMI and/or low FFMI) among our COPD patients was 22.2%. Mean FFMI was significantly lower in normal or underweight patients versus overweight or obese patients. Patients with low FFMI had lower exercise capacity at the 6MWT and higher CAT scores than patients with normal FFMI.
Depending on the BMI and FFMI values the patients were divided in four categories: normal, semistarvation, sarcopenia and cachexia. The group of patients with sarcopenia (low FFMI and normal BMI) had the lowest mean MIP (Maximal Inspiratory Pressure), the lowest mean 6MWD (six minutes walking distance) and the higher CAT mean scores among all groups. Exercise capacity was significantly lower in muscular depleted patients (with low skeletal muscle mass index - SSMI). MIP correlated significantly with FFMI and SMMI. No correlations were found between parameters of body composition and FEV1 or CAT. Segmental body composition assessment revealed that unbalanced upper/lower skeletal muscle mass is associated with a lower exercise capacity as measured by 6WMT.
Conclusions:
This study offers the first data on body composition of Romanian COPD patients. The prevalence of nutritional depletion is similar to that found in other European studies. No significant correlations were found between FFMI and severity of the disease (bronchial obstruction, distance walked, CAT score). FFMI and SSMI correlated significantly with MIP. Sarcopenic patients had the lowest mean 6MWD, the lowest mean MIP and the highest CAT mean scores. SMMI significantly correlated with 6MWD. Segmental body composition assessment of revealed that "unbalanced" patients had lower results at 6MWT. These results show that body composition evaluation is useful for the assessment of COPD patients referred to pulmonary rehabilitation and should be routinely performed
PMCID: PMC4268286  PMID: 25553122
body composition; chronic obstructive pulmonary disease; pulmonary rehabilitation
25.  Elevated plasma leptin concentrations in early stages of experimental intestinal inflammation in rats 
Gut  1998;43(6):783-790.
Background—Although leptin, an adipocyte derived hormone which regulates food intake and energy balance, is released after injections of tumour necrosis factor (TNF) and interleukin 1,plasma concentrations have not been characterised in chronic inflammation. Leptin may contribute to the anorexia and body weight loss associated particularly with the acute stages of inflammatory bowel disease. 
Aims—To investigate plasma leptin concentrations during the time course of intestinal inflammation in different animal models. 
Methods—Plasma leptin was measured at different time points in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis, indomethacin induced ileitis, or endotoxic shock caused by lipopolysaccharide (LPS). Systemic TNF-α was also measured during acute inflammation. 
Results—Plasma leptin concentrations increased fourfold eight hours after induction of TNBS colitis (p<0.0001) and twofold after administration of ethanol alone (p<0.02). Plasma leptin responses throughout the first post-treatment day were correlated with myeloperoxidase activity and gross damage scores. Similar leptin overexpression was observed in indomethacin induced ileitis and in rats with endotoxic shock. Plasma concentrations were lower in TNBS treated rats than in controls on day 5 before reaching a similar concentration on day 14. Anorexia and body weight loss were observed during the first four days post-TNBS. A significant increase in systemic TNF-α was only detected in LPS treated rats. 
Conclusion—Elevated plasma leptin concentrations, correlated with the degree of inflammation and associated with anorexia, were induced in rats during the early stages of experimental intestinal inflammation but proved transient; this might account for discrepancies in recent results concerning concentrations in patients with inflammatory bowel diseases. 


Keywords: leptin; inflammatory bowel disease; experimental rat intestinal inflammation; tumour necrosis factor; endotoxic shock; anorexia
PMCID: PMC1727345  PMID: 9824605

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