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.

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.

Nutritional support and functional capacity in chronic obstructive pulmonary disease: A systematic review and meta-analysis

Currently there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCTs (n = 448) in stable COPD patients investigating the effects of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 10 RCTs), enteral tube feeding (1 RCT)] versus control on functional outcomes. Meta-analysis of the changes induced by intervention found that whilst respiratory function (FEV(1,) lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (PI max +3.86 SE 1.89 cm H(2) O, P = 0.041; PE max +11.85 SE 5.54 cm H(2) O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved, and associated with weight gains of ≥ 2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta-analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta-analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.

Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease

Deleterious responses to pathogens during infancy may contribute to infection and associated asthma. Chlamydia respiratory infections in early life are common causes of pneumonia and lead to reduced lung function and asthma. We investigated the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory infection, infection-induced airway hyperresponsiveness (AHR), and severe allergic airway disease (AAD). Infected infant Il13−/− mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13−/− mice induced persistent AHR. Infection and associated pathology were restored in infected Il13−/− mice by reconstitution with IL-13. Stat6−/− mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.

Nutritional support in chronic obstructive Pulmonary Disease (COPD) a randomised trial

Rationale Nutritional support is effective in managing malnutrition in COPD (Collins et al., 2012) leading to functional improvements (Collins et al., 2013). However, comparative trials of first line interventions are lacking. This randomised trial compared the effectiveness of individualised dietary advice by a dietitian (DA) versus oral nutritional supplements (ONS). Methods A target sample of 200 stable COPD outpatients at risk of malnutrition (‘MUST’; medium + high risk) were randomised to either a 12-week intervention of ONS (ONS: ~400 kcal/d, ~40 g/d protein) or DA with supportive written advice. The primary outcome was quality of life (QoL) measured using St George’s Respiratory Questionnaire with secondary outcomes including handgrip strength, body weight and nutritional intake. Both the change from baseline and the differences between groups was analysed using SPSS version 20. Results 84 outpatients were recruited (ONS: 41 vs. DA: 43), 72 completed the intervention (ONS: 33 vs. DA: 39). Mean BMI was 18.2 SD 1.6 kg/m2, age 72.6 SD 10 years, FEV1% predicted 36 SD 15% (severe COPD). In comparison to the DA group, the ONS group experienced significantly greater improvements in protein intakes above baseline values at both week 6 (+21.0 SEM 4.3 g/d vs. +0.52 SEM 4.3 g/d; p < 0.001) and week 12 (+19.0 SEM 5.0 g/d vs. +1.0 SEM 3.6 g/d; p = 0.033;ANOVA). QoL and secondary outcomes remained stable at 12 weeks in both groups with slight improvements in the ONS group but no differences between groups. Conclusion In outpatients at risk of malnutrition with severe COPD, nutritional support involving either ONS or DA appears to maintain in tritional status, functional capacity and QoL. However, larger trials, and earlier, multi-modal nutritional interventions for an extended duration should be explored.

The effectiveness of dietary counselling versus oral nutrition supplements in improving nutritional intake in malnourished patients with Chronic Obstructive Pulmonary Disease (COPD)

The evidence for nutritional support in COPD is almost entirely based on oral nutritional supplements (ONS) yet despite this dietary counseling and food fortification (DA) are often used as the first line treatment for malnutrition. This study aimed to investigate the effectiveness of ONS vs. DA in improving nutritional intake in malnourished outpatients with COPD. 70 outpatients (BMI 18.4 SD 1.6 kg/m2, age 73 SD 9 years, severe COPD) were randomised to receive a 12-week intervention of either ONS or DA (n 33 ONS vs. n 37 DA). Paired t-test analysis revealed total energy intakes significantly increased with ONS at week 6 (+302 SD 537 kcal/d; p = 0.002), with a slight reduction at week 12 (+243 SD 718 kcal/d; p = 0.061) returning to baseline levels on stopping supplementation. DA resulted in small increases in energy that only reached significance 3 months post-intervention (week 6: +48 SD 623 kcal/d, p = 0.640; week 12: +157 SD 637 kcal/d, p = 0.139; week 26: +247 SD 592 kcal/d, p = 0.032). Protein intake was significantly higher in the ONS group at both week 6 and 12 (ONS: +19.0 SD 25.0 g/d vs. DA: +1.0 SD 13.0 g/d; p = 0.033 ANOVA) but no differences were found at week 26. Vitamin C, Iron and Zinc intakes significantly increased only in the ONS group. ONS significantly increased energy, protein and several micronutrient intakes in malnourished COPD patients but only during the period of supplementation. Trials investigating the effects of combined nutritional interventions are required.

The effect of deprivation and disease-severity on malnutrition risk in chronic obstructive pulmonary disease (COPD)

Deprivation has previously been shown to be an independent risk factor for the high prevalence of malnutrition observed in COPD (Collins et al., 2010). It has been suggested the socioeconomic gradient observed in COPD is greater than any other chronic disease (Prescott & Vestbo, 1999). The current study aimed to examine the infl uence of disease severity and social deprivation on malnutrition risk in outpatients with COPD. 424 COPD outpatients were screened using the ‘Malnutrition Universal Screening Tool’ (‘MUST’). COPD disease severity was recorded in accordance with the GOLD criteria and deprivation was established according to the patient’s geographical location (postcode) at the time of nutritional screening using the UK Government’s Index of Multiple Deprivation (IMD). IMD ranks postcodes from 1 (most deprived) to 32,482 (least deprived). Disease severity was posi tively associated with an increased prevalence of malnutrition risk (p < 0.001) both within and between groups, whilst rank IMD was negatively associated with malnutrition (p = 0.020), i.e. those residing in less deprived areas were less likely to be malnourished. Within each category of disease severity the prevalence of malnutrition was two-fold greater in those residing in the most deprived areas compared to those residing in the least deprived areas. This study suggests that deprivation and disease severity are independent risk factors for malnutrition in COPD both contributing to the widely variable prevalence of malnutrition. Consideration of these issues could assist with the targeted nutritional management of these patients.

Evaluation of immune responses to influenza vaccination in chronic obstructive pulmonary disease

Background: Given that viral infections are common triggers for exacerbations of Chronic Obstructive Pulmonary Disease (COPD), current clinical guidelines recommend that all patients receive annual influenza vaccinations. A detailed examination of the immune response to vaccination in COPD has not previously been undertaken, so this study aimed to compare immune responses to influenza vaccination between COPD patients and healthy subjects. Methods: Twenty one COPD patients and fourteen healthy subjects were recruited and cellular immune function was assessed pre- and post- vaccination with trivalent inactivated influenza vaccine. Results: One month after vaccination, H1N1 specific antibody titres were significantly lower in COPD patients than in healthy controls (p=0.02). Multivariate analysis demonstrated that post vaccination antibody titres were independently associated with COPD, but not with age or smoking status. Innate immune responses to the vaccine preparation did not differ between the two populations. Serum concentrations of IL-21, a cytokine that is important for B cell development and antibody synthesis, were also lower in COPD patients than in healthy subjects (p<0.01). In vitro functional differences were also observed, with fewer proliferating B cells expressing CD27 (p=0.04) and reduced T-cell IFN-γ synthesis (p<0.01) in COPD patients, relative to healthy subjects. Conclusions: In conclusion, COPD was associated with altered immune responses to influenza vaccination compared to healthy controls with reductions in both T-cell and B-cell function. These findings provide a foundation for future research aimed at optimising the effectiveness of influenza vaccination in COPD.

Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study

Background: Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians. However, this issue still remained controversial. Additional evidence