Anorexia in chronic obstructive pulmonary disease — Association to cachexia and hormonal derangement

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Abstract

Background

In patients with chronic obstructive pulmonary disease (COPD) weight loss frequently occurs that may ultimately lead to cachexia as a serious co-morbidity, indicating severely impaired functional capacity, health status and increased mortality. Increased energy expenditure due to mechanic and metabolic inefficiency and systemic inflammation are determinants of a hypermetabolic state that is not balanced by dietary intake. Anorexia may importantly contribute to weight loss in COPD, however, the association between immune and hormonal derangement and altered appetite has not been studied in detail.

Aim

The aim of the present study was to investigate whether anorexia in COPD is related to inflammation and hormonal derangement in association to weight loss.

Methods

We prospectively enrolled 103 consecutive patients with COPD (age 59.8 ± 1.3 years, 35% female, mean FEV1 38.3 ± 1.7%) in comparison to healthy controls of similar age (n = 15).

Results

In 34 patients (33%) cachexia was diagnosed (weight loss > 7.5%, BMI  24 kg/m2). Cachectic COPD patients had lower BMI (19.0 ± 0.5 vs 25.6 ± 0.7 kg/m2) and impaired lung function (FEV1 31 ± 2% vs 42 ± 2%, FVC 51 ± 3 vs 59 ± 3%, both p < 0.001). Inflammatory immune activation (IL-6 and IL-6/IL-10 ratio) was significantly higher in cachectic COPD patients. Analysis of the extent of anorexia (visual analogue scale) revealed that cachectic COPD patients had significantly decreased subjective desire to eat compared to non-cachectic patients (3.5 ± 0.3 vs 6.3 ± 0.2, p < 0.001). Patients with COPD and cachexia showed evidence of acquired GH resistance (decreased IGF-1/GH ratio) and insulin resistance (HOMA). Anorexia showed a direct correlation with the IGF-1/GH ratio (r = 0.34, p < 0.05) and was further related to BMI and % weight loss (both p < 0.001).

Conclusion

In COPD anorexia relates to hormonal derangement and inflammatory immune activation. Anorexia contributes to development of cachexia. The concept of appetite stimulating therapy emerges as a novel therapeutic option in cachectic COPD patients.

Introduction

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease. In the chronic course of the disease, the pathogenesis and clinical manifestations of COPD are not restricted to pulmonary structural and functional impairment but rather have multi-systemic implications including metabolic, hormonal and organ dysfunction such as in skeletal muscle, heart, brain and skeleton [1]. Weight loss due to tissue wasting is frequent in COPD and may ultimately lead to cachexia as a serious co-morbidity in advanced disease state. Cachexia in COPD – as in other chronic diseases – is associated with a greater susceptibility to exacerbation of clinical symptoms, with severely impaired functional capacity [2], poor health status and quality of life [3], [4]. The loss of skeletal muscle tissue and, in particular, of respiratory muscle is associated with a loss of power and endurance leading to a further mechanical impairment of lung function with consecutive hypoxia and hypercapnia [5]. This may contribute to progression of the disease. Accordingly, increasing evidence suggests that weight loss and cachexia are independent prognostic factors in COPD [6], [7].

Weight loss in COPD is a consequence of increased energy expenditure due to mechanic and metabolic inefficiency that is not balanced by adequately increased energy supply. Inflammatory activation and hormonal derangements may further add to a hypermetabolic state and an overall catabolic/anabolic imbalance leading to depletion of endogenous energy storages and eventually to structural tissue degradation.

The regulation of energy expenditure in association to inflammatory activation and hormonal derangement in COPD patients has widely been studied [8], [9], [10], [11], [12]. Anorexia may importantly contribute to weight loss in COPD. The therapeutic concept, however, of nutritional supplementation failed to show significant effects on anthropometric measures and functional capacity in these patients [13] and mechanisms of non-response to nutritional therapy have been discussed [14]. In this context, the significance of alteration in appetite as a central regulator of food intake has not been studied in detail.

In the current study we prospectively assessed in a cohort of COPD patients with and without weight loss the extent of anorexia in relationship to alteration in body weight. The specific association to hormonal and inflammatory parameters in order to identify potential factors that may influence appetite in COPD is taken into account.

Section snippets

Patient population

We recruited 103 consecutive patients (age 59.8 ± 1.3 years, 36 female [35%]) diagnosed with COPD by history, physical examination and pulmonary function test, according to the guidelines of the American Thoracic Society [15]. All patients showed a FEV1 reversibility of less than 15% in response to inhaled bronchodilators. At time of investigation, all patients were clinically stable without signs of acute exacerbation. No patient had required hospital admission or treatment change during the

Patient characteristics

The main clinical characteristics of the study population are presented in Table 1. COPD Patients and control subjects were similar for age and global parameters of body composition but patients had impaired respiratory function parameters. Comparing patient subgroups of cachectic and non-cachectic patients, COPD patients with cachexia showed further decreased respiratory (FEV1, FVC, and FEV1/FVC; all p < 0.05). Age, height and drug therapy were similar between subgroups (p > 0.2).

Analysis of anorexia

The analysis of

Discussion

This study demonstrates a significant prevalence of cachexia occurring in COPD and shows that anorexia is frequently present in patients with COPD and cachexia. The degree of appetite in COPD patients is related to body mass index, inflammation and catabolic/anabolic imbalance.

The pathogenesis and clinical manifestations of COPD are not restricted to pulmonary inflammation and airway remodelling [18]. Involuntary weight loss occurs frequently in a significant number of patients, particularly in

References (31)

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