The 'obesity paradox' in chronic obstructive pulmonary disease

Poor nutritional status in chronic obstructive pulmonary disease (COPD) is associated with increased mortality independently of disease-severity (Collins et al).1 Epidemiological studies have suggested a protective role of obesity against mortality in COPD (Vestbo et al)2 which is contrary to data from the general population where obesity is associated with decreased life expectancy. This relationship has been referred to as the ‘obesity paradox’ and has been demonstrated in a number of chronic wasting conditions (Kalantar-Zadeh et al).3 This study investigated the existence of the obesity paradox in outpatients with COPD by examining the effect of body mass index (BMI) on 1-year healthcare use and clinical outcome in terms of hospital admission rates, length of hospital stay, outpatient appointments and mortality. BMI was assessed in 424 outpatients with COPD, with measurements performed by specialist respiratory nurses during outpatient clinics. 1-year healthcare use was retrospectively collected from the date of BMI measurement. Abstract S163 Table 1 Patients classified as overweight (25.0–29.9 kg/m2) or obese (>30 kg/m2) experienced significantly fewer emergency hospital admissions, as well as a reduced length of hospital stay, in comparison to normal weight (20.0–24.9 kg/m2) or underweight (<20 kg/m2) outpatients. There was a significant negative trend between BMI classification and mortality. This study supports the existence of the ‘obesity paradox’ in COPD, not only in relation to reduced 1 year mortality rates but also in terms of reduced emergency hospital admissions and reduced length of hospital stay.

P147 Deprivation is associated with increased healthcare utilisation in patients with chronic obstructive pulmonary disease

Deprivation assessed using the index of multiple deprivation (IMD) has been shown to be an independent risk factor for 1-year mortality in outpatients with chronic obstructive pulmonary disease; COPD (Collins et al, 2010). IMD combines a number of economic and social issues (eg, health, education, employment) into one overall deprivation score, the higher the score the higher an individual's deprivation. Whilst malnutrition in COPD has been linked to increased healthcare use it is not clear if deprivation is also independently associated. This study aimed to investigate the influence of deprivation on 1-year healthcare utilisation in outpatients with COPD. IMD was established in 424 outpatients with COPD according to the geographical location for each patient's address (postcode) and related to their healthcare use in the year post-date screened (Nobel et al, 2008). Patients were routinely screened in outpatient clinics for malnutrition using the ‘Malnutrition Universal Screening Tool’, ‘MUST’ (Elia 2003); mean age 73 (SD 9.9) years; body mass index 25.8 (SD 6.3) kg/m2 with healthcare use collected 1 year from screening (Abstract P147 Table 1). Deprivation assessed using IMD (mean 15.9; SD 11.1) was found to be a significant predictor for the frequency and duration of emergency hospital admissions as well as the duration of elective hospital admission. Deprivation was also linked to reduced secondary care outpatient appointment attendance but not an increase in failure to attend and deprivation was not associated with increased disease severity, as classified by the GOLD criteria (p=0.580). COPD outpatients residing in more deprived areas experience increased hospitalisation rates but decreased outpatient appointment attendance. The underlying reason behind this disparity in healthcare use requires further investigation.

Nutritional support in chronic obstructive pulmonary disease: a systematic review and meta-analysis

BACKGROUND: The efficacy of nutritional support in the management of malnutrition in chronic obstructive pulmonary disease (COPD) is controversial. Previous meta-analyses, based on only cross-sectional analysis at the end of intervention trials, found no evidence of improved outcomes. OBJECTIVE: The objective was to conduct a meta-analysis of randomized controlled trials (RCTs) to clarify the efficacy of nutritional support in improving intake, anthropometric measures, and grip strength in stable COPD. DESIGN: Literature databases were searched to identify RCTs comparing nutritional support with controls in stable COPD. RESULTS: Thirteen RCTs (n = 439) of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 11 RCTs), and enteral tube feeding (1 RCT)] with a control comparison were identified. An analysis of the changes induced by nutritional support and those obtained only at the end of the intervention showed significantly greater increases in mean total protein and energy intakes with nutritional support of 14.8 g and 236 kcal daily. Meta-analyses also showed greater mean (±SE) improvements in favor of nutritional support for body weight (1.94 ± 0.26 kg, P < 0.001; 11 studies, n = 308) and grip strength (5.3%, P < 0.050; 4 studies, n = 156), which was not shown by ANOVA at the end of the intervention, largely because of bias associated with baseline imbalance between groups. CONCLUSION: This systematic review and meta-analysis showed that nutritional support, mainly in the form of ONS, improves total intake, anthropometric measures, and grip strength in COPD. These results contrast with the results of previous analyses that were based on only cross-sectional measures at the end of intervention trials.

The influence of smoking status on malnutrition risk and 1-year mortality in outpatients with chronic obstructive pulmonary disease.

Introduction:  Smoking status in outpatients with chronic obstructive pulmonary disease (COPD) has been associated with a low body mass index (BMI) and reduced mid-arm muscle circumference (Cochrane & Afolabi, 2004). Individuals with COPD identified as malnourished have also been found to be twice as likely to die within 1 year compared to non-malnourished patients (Collins et al., 2010). Although malnutrition is both preventable and treatable, it is not clear what influence current smoking status, another modifiable risk factor, has on malnutrition risk. The current study aimed to establish the influence of smoking status on malnutrition risk and 1-year mortality in outpatients with COPD. Methods:  A prospective nutritional screening survey was carried out between July 2008 and May 2009 at a large teaching hospital (Southampton General Hospital) and a smaller community hospital within Hampshire (Lymington New Forest Hospital). In total, 424 outpatients with a diagnosis of COPD were routinely screened using the ‘Malnutrition Universal Screening Tool’, ‘MUST’ (Elia, 2003); 222 males, 202 females; mean (SD) age 73 (9.9) years; mean (SD) BMI 25.9 (6.4) kg m−2. Smoking status on the date of screening was obtained for 401 of the outpatients. Severity of COPD was assessed using the GOLD criteria, and social deprivation determined using the Index of Multiple Deprivation (Nobel et al., 2008). Results:  The overall prevalence of malnutrition (medium + high risk) was 22%, with 32% of current smokers at risk (who accounted for 19% of the total COPD population). In comparison, 19% of nonsmokers and ex-smokers were likely to be malnourished [odds ratio, 1.965; 95% confidence interval (CI), 1.133–3.394; P = 0.015]. Smoking status remained an independent risk factor for malnutrition even after adjustment for age, social deprivation and disease-severity (odds ratio, 2.048; 95% CI, 1.085–3.866; P = 0.027) using binary logistic regression. After adjusting for age, disease severity, social deprivation, smoking status, malnutrition remained a significant predictor of 1-year mortality [odds ratio (medium + high risk versus low risk), 2.161; 95% CI, 1.021–4.573; P = 0.044], whereas smoking status did not (odds ratio for smokers versus ex-smokers + nonsmokers was 1.968; 95% CI, 0.788–4.913; P = 0.147). Discussion:  This study highlights the potential importance of combined nutritional support and smoking cessation in order to treat malnutrition. The close association between smoking status and malnutrition risk in COPD suggests that smoking is an important consideration in the nutritional management of malnourished COPD outpatients. Conclusions:  Smoking status in COPD outpatients is a significant independent risk factor for malnutrition and a weaker (nonsignificant) predictor of 1-year mortality. Malnutrition significantly predicted 1 year mortality. References:  Cochrane, W.J. & Afolabi, O.A. (2004) Investigation into the nutritional status, dietary intake and smoking habits of patients with chronic obstructive pulmonary disease. J. Hum. Nutr. Diet.17, 3–11. Collins, P.F., Stratton, R.J., Kurukulaaratchym R., Warwick, H. Cawood, A.L. & Elia, M. (2010) ‘MUST’ predicts 1-year survival in outpatients with chronic obstructive pulmonary disease. Clin. Nutr.5, 17. Elia, M. (Ed) (2003) The ‘MUST’ Report. BAPEN. http://www.bapen.org.uk (accessed on March 30 2011). Nobel, M., McLennan, D., Wilkinson, K., Whitworth, A. & Barnes, H. (2008) The English Indices of Deprivation 2007. http://www.communities.gov.uk (accessed on March 30 2011).

Deprivation is an independent predictor of 1-year mortality in outpatients with chronic obstructive pulmonary disease

Deprivation is linked to increased incidence in a number of chronic diseases but its relationship to chronic obstructive pulmonary disease (COPD) is uncertain despite suggestions that the socioeconomic gradient seen in COPD is as great, if not greater, than any other disease (Prescott and Vestbo).1 There is also a need to take into account the confounding effects of malnutrition which have been shown to be independently linked to increased mortality (Collins et al).2 The current study investigated the influence of social deprivation on 1-year survival rates in COPD outpatients, independently of malnutrition. 424 outpatients with COPD were routinely screened for malnutrition risk using the ‘Malnutrition Universal Screening Tool’; ‘MUST’ (Elia),3 between July and May 2009; 222 males and 202 females; mean age 73 (SD 9.9) years; body mass index 25.8 (SD 6.3) kg/m2. Each individual's deprivation was calculated using the index of multiple deprivation (IMD) which was established according to the geographical location of each patient's address (postcode). IMD includes a number of indicators covering economic, housing and social issues (eg, health, education and employment) into a single deprivation score (Nobel et al).4 The lower the IMD score, the lower an individual's deprivation. The IMD was assigned to each outpatient at the time of screening and related to1-year mortality from the date screened. Outpatients who died within 1-year of screening were significantly more likely to reside within a deprived postcode (IMD 19.7±SD 13.1 vs 15.4±SD 10.7; p=0.023, OR 1.03, 95% CI 1.00 to 1.06) than those that did not die. Deprivation remained a significant independent risk factor for 1-year mortality even when adjusted for malnutrition as well as age, gender and disease severity (binary logistic regression; p=0.008, OR 1.04, 95% CI 1.04 to 1.07). Deprivation was not associated with disease-severity (p=0.906) or body mass index, kg/m2 (p=0.921) using ANOVA. This is the first study to show that deprivation, assessed using IMD, is associated with increased 1-year mortality in outpatients with COPD independently of malnutrition, age and disease severity. Deprivation should be considered in the targeted management of these patients.

The influence of deprivation domains on malnutrition risk in outpatients with chronic obstructive pulmonary disease

Deprivation assessed using the Index of Multiple Deprivation (IMD) has been shown to be an independent risk factor for both malnutrition and mortality in outpatients with chronic obstructive pulmonary disease (COPD) (Collins et al., 2010a, b). IMD consists of a range of different deprivation domains, although it is unclear which ones are most closely linked to malnutrition. The aim of the current study was to investigate whether the relationship between malnutrition and deprivation was a general one, affecting all domains in a consistent manner, or specific, affecting only certain domains.

Improved treatment of nicotine addiction and emerging pulmonary drug delivery

Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders.

Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery : a review for multidisciplinary researchers

Pulmonary drug delivery is the focus of much research and development because of its great potential to produce maximum therapeutic benefit. Among the available options the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse number of diseases. However, as drug delivery from a DPI involves a complicated set of physical processes and the integration of drug formulations, device design and patient usage, the engineering development of this medical technology is proving to be a great challenge. Currently there is large range of devices that are either available on the market or under development, however, none exhibit superior clinical efficacy. A major concern is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs. The extent of variability depends on the drug formulation, the device design and the patient’s inhalation profile. This article reviews recent advances in DPI technology and presents the key factors which motivate and constrain the successful engineering of a universal, patient-independent DPI that is capable of efficient, reliable and repeatable drug delivery. A strong emphasis is placed on the physical processes of drug powder aerosolisation, deagglomeration, and dispersion and on the engineering of formulations and inhalers that can optimise these processes.

Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients.

Alterations in innate immunity that predispose to chronic obstructive pulmonary disease (COPD) exacerbations are poorly understood. We examined innate immunity gene expression in peripheral blood polymorphonuclear leukocytes (PMN) and monocytes stimulated by Haemophilus influenzae and Streptococcus pneumoniae. Thirty COPD patients (15 rapid and 15 non-rapid lung function decliners) and 15 smokers without COPD were studied. Protein expression of IL-8, IL-6, TNF-α and IFN-γ (especially monocytes) increased with bacterial challenge. In monocytes stimulated with S. pneumoniae, TNF-α protein expression was higher in COPD (non-rapid decliners) than in smokers. In co-cultures of monocytes and PMN, mRNA expression of TGF-β1 and MYD88 was up-regulated, and CD14, TLR2 and IFN-γ down-regulated with H. influenzae challenge. TNF-α mRNA expression was increased with H. influenzae challenge in COPD. Cytokine responses were similar between rapid and non-rapid decliners. TNF-α expression was up-regulated in non-rapid decliners in response to H. influenzae (monocytes) and S. pneumoniae (co-culture of monocytes and PMN). Exposure to bacterial pathogens causes characteristic innate immune responses in peripheral blood monocytes and PMN in COPD. Bacterial exposure significantly alters the expression of TNF-α in COPD patients, although not consistently. There did not appear to be major differences in innate immune responses between rapid and non-rapid decliners.