Respiratory Medicine: COPD Update最新文献

Chronic Obstructive Pulmonary disease (COPD) is associated with multiple comorbid conditions including ischemic heart disease, peripheral muscular dysfunction, osteoporosis, osteopenia, glaucoma, anemia, anxiety , depression, caquexia and malnutrition. A number of individuals with COPD experience involuntary weight loss as the condition progresses and weight loss, muscle wasting and tissue depletion are commonly seen.

Malnutrition has a negative impact on the clinical course of COPD. The negative impact of malnutrition has led to interest in nutritional assessment and supplementation, alone or in combination with anabolic substances or appetite stimulants, in an effort to improve disease outcome. The effects of nutritional supplementation on weigh gain and anthropometric parameters were small suggesting that oral supplementation alone is of limited efficacy. The studies with anabolic steroids or growth hormone showed improvement in nutritional parameters but no improvement in exercise capacity.

Large randomized trials that include measure of lean body mass, exercise capacity and quality of life should be stimulated.

Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the lower airways of patients with chronic obstructive pulmonary disease (COPD). Whether it contributes to COPD progression is unknown. Here, we determined which aspects of the COPD phenotype can be induced by repetitive exposure to NTHi products. Mice were exposed weekly to an aerosolized NTHi lysate, and inflammation was evaluated by measurement of cells and cytokines in bronchoalveolar lavage fluid (BALF) and immunohistochemical staining; structural changes were evaluated histochemically by periodic acid fluorescent Schiff's reagent, Masson's trichrome, and Picrosirius red staining; mucin gene expression was measured by quantitative RT-PCR; and the role of TNF-α was examined by transgenic airway overexpression and use of an inhibitory antibody. NTHi lysate induced rapid activation of NF-kappaB in airway cells and increases of inflammatory cytokines and neutrophils in BALF. Repetitive exposure induced infiltration of macrophages, CD8+ T cells, and B cells around airways and blood vessels, and collagen deposition in airway and alveolar walls, but airway mucin staining and gel-forming mucin transcripts were not increased. Transgenic overexpression of TNF-α caused BALF neutrophilia and inflammatory cell infiltration around airways, but not fibrosis, and TNF-α neutralization did not reduce BALF neutrophilia in response to NTHi lysate. In conclusion, NTHi products elicit airway inflammation in mice with a cellular and cytokine profile similar to that in COPD, and cause airway wall fibrosis but not mucous metaplasia. TNF-α is neither required for inflammatory cell recruitment nor sufficient for airway fibrosis. Colonization by NTHi may contribute to the pathogenesis of small airways disease in patients with COPD.

Reproduced with permission from the American Thoracic Society.

Rationale

Although chronic obstructive pulmonary disease is the first indication for lung transplantation, the benefit of the procedure in terms of survival remains debated.

Objectives

To estimate the determinants of the survival benefit of lung transplantation in patients with chronic obstructive pulmonary disease.

Methods

Using information from the United Network for Organ Sharing database on 8182 patients, we developed an approach based on numerical simulations to estimate the survival effect of lung transplantation.

Measurements and main results

The main outcome measure was the difference between median survival with transplantation and that without transplantation measured from time of transplant list registration. Survival benefit was greater with double than with single lung transplantation (mean difference, 307 d [95% confidence interval, 217–523]). With double lung transplantation, 44.6% of patients would gain 1 year or more, 29.4% would gain or lose less than 1 year, and 26% would lose 1 year or more. Major determinants of the survival effect of transplantation were systolic pulmonary artery pressure, FEV₁, body mass index, exercise capacity, functional status, and the need for continuous mechanical ventilation or oxygen. For instance, 79% of patients with an FEV₁ less than 16% of the predicted value would gain 1 year or more with double lung transplantation as compared with only 11% of patients with an FEV₁ of more than 25%.

Conclusions

We identified several factors associated with the survival benefit of lung transplantation. External validation of our models is required before translating these results into clinical practice.

Reproduced with permission from the American Thoracic Society.