抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Global strategy for asthma management and prevention

Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

/pdf/how-do-glucocorticoids-influence-stress-responses-4egr3fa2k0.pdf

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Asthma is successfully treated in most patients through the use of conventional corticosteroid therapy. The majority (90 to 95%) of patients respond effectively to moderate doses of inhaled corticosteroids with minimal side effects. Nevertheless, there is a small population of asthmatic patients, including present and ex-cigarette smokers, who fail to respond adequately to corticosteroid treatment even at high doses or with the addition of supplementary therapy. These patients account for a disproportionate amount of healthcare costs because they exacerbate more frequently and are more likely to be admitted to hospital due to their asthma. Cigarette smoking is an important factor associated with corticosteroid resistance in asthmatics, and there is scope for the development of novel therapies to target this subgroup of asthmatics. This review summarizes the various hypotheses underlying corticosteroid insensitivity in smoking asthmatics and discusses the development of potential novel therapies based on these concepts.

Overcoming steroid insensitivity in smoking asthmatics.

Neuroimmune Interactions in the Lung

Clinical outcome of adding long-acting β-agonists to inhaled corticosteroids

1. The effects of a new long-acting inhaled beta 2-adrenoceptor agonist aerosol formoterol (12 micrograms), on FEV1, and on methacholine-induced bronchoconstriction, were compared with those of terbutaline (250 micrograms) and placebo in 12 midly asthmatic subjects. 2. PC20, the concentration of methacholine needed to cause a 20% fall in baseline FEV1, was determined 2 and 5 h after formoterol, terbutaline and placebo on separate days. Baseline PC20 was determined on a different day. 3. Compared with terbutaline and placebo, formoterol hastened recovery from methacholine-induced bronchoconstriction, and significantly increased mean PC20 (by 2.2- and 2.9-fold at 2 and 5 h respectively). 4. Thus, formoterol has a protective effect against methacholine-induced bronchoconstriction which lasts for at least 5 h.

Effect of formoterol, a long‐lasting beta 2‐adrenoceptor agonist, against methacholine‐induced bronchoconstriction.

World COPD Day organized by GOLD (Global Initiative for Chronic Obstructive Lung Disease) is celebrated on November 18th this year to again raise awareness of this common but still neglected disease. Is seems barely credible that COPD is so poorly recognized by the general public and even many healthcare professionals, especially as it is the only common chronic disease that has steadily increased over the last 50 years and is now the third ranked cause of death after cardiovascular disease and stroke (18). The costs of COPD, which affects over 400 million people in the world, are mind-blowing—the World Economic Forum has estimated that the global costs of COPD will reach US$50 trillion/yr by 2030, making it more costly than cardiovascular disease (13). Yet not only is COPD largely ignored, there is very little research funding available compared with cancer, cardiovascular disease, and neurological diseases. We do have more effective therapies, and particularly long-acting inhaled bronchodilators, and GOLD has been very successful in promoting more effective assessment and management of the disease, but we still do not have any therapy that has been shown to reduce its relentless progression and no drugs that have a major impact on mortality or comorbidities. This may reflect the fact that there is still a poor understanding of the underlying disease mechanisms.

https://journals.physiology.org/doi/pdf/10.1152/ajplung.00473.2020

Peter J. Barnes

Papers

Overcoming steroid insensitivity in smoking asthmatics.

Neuroimmune Interactions in the Lung

Clinical outcome of adding long-acting β-agonists to inhaled corticosteroids

Effect of formoterol, a long‐lasting beta 2‐adrenoceptor agonist, against methacholine‐induced bronchoconstriction.

COPD 2020: new directions needed.