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

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

Efforts to understand and mitigate the health effects of particulate matter (PM) air pollution have a rich and interesting history. This review focuses on six substantial lines of research that have been pursued since 1997 that have helped elucidate our understanding about the effects of PM on human health. There has been substantial progress in the evaluation of PM health effects at different time-scales of exposure and in the exploration of the shape of the concentration-response function. There has also been emerging evidence of PM-related cardiovascular health effects and growing knowledge regarding interconnected general pathophysiological pathways that link PM exposure with cardiopulmonary morbidity and mortality. Despite important gaps in scientific knowledge and continued reasons for some skepticism, a comprehensive evaluation of the research findings provides persuasive evidence that exposure to fine particulate air pollution has adverse effects on cardiopulmonary health. Although much of this research has been motivated by environmental public health policy, these results have important scientific, medical, and public health implications that are broader than debates over legally mandated air quality standards.

/pdf/health-effects-of-fine-particulate-air-pollution-lines-that-s831sp8jap.pdf

Health effects of fine particulate air pollution: lines that connect

A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.

/pdf/the-human-microbiome-project-1armeyuv2c.pdf

The human microbiome project.

We determined the prevalence of markers of atopy and asthma among 1,199 rural secondary school students ages 12 to 19 yr. Subjects identified as having been raised on a farm and half as many subjects without regular exposure to a farming environment from the same school class completed a respiratory symptom questionnaire and underwent allergy skin tests and a methacholine bronchoprovocation test. Current wheeze, airways hyperresponsiveness (AHR), and skin test positivity to inhaled allergens were all significantly less common among adolescents raised on the farm and these differences were especially pronounced in girls. After adjusting for gender and current smoking, the odds ratios for being raised on a farm were: 0.70 (95% CI 0.52 to 0.95) for current wheeze; 0.59 (95% CI 0.37 to 0.95) for asthma, defined as the concomitant occurrence of wheeze and AHR; and 0.58 (95% CI 0.46 to 0.75) for atopy defined as a positive reaction to any one of 24 common inhaled allergens. These associations were also not sign...

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.5.9908119

Relative Scarcity of Asthma and Atopy among Rural Adolescents Raised on a Farm

Background Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. Objective We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. Methods Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle α-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. Results ASM area was greater in subjects with severe (0.24 ± 0.03 mm 2 ) than in subjects with moderate (0.05 ± 0.01 mm 2 ) asthma ( P P Conclusion Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma.

Differences in airway remodeling between subjects with severe and moderate asthma.

Background: Inhaled corticosteroids are effective at preventing asthma morbidity and mortality. Most studies, however, have focused on short term effects, raising uncertainty about their effectiveness in the long term. Methods: The Saskatchewan Health databases were used to form two population based cohorts of asthma patients aged 5–44 between 1975 and 1991. The first cohort included all subjects from the start of asthma treatment, while the second included subjects hospitalised for asthma from the date of discharge. Subjects were followed up, starting 1 year after cohort entry and continuing until 1997, 54 years of age, or death. The outcome was the first asthma hospital admission and readmission, respectively, to occur during follow up. A nested case-control design was used by which all cases were matched on calendar time and several markers of asthma severity to all available controls within the cohort. Results: The full cohort included 30 569 asthmatic subjects of which 3894 were admitted to hospital for asthma and 1886 were readmitted. The overall rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to 43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction found during the first 4 years of follow up was sustained over the longer term. Regular use of inhaled corticosteroids can potentially prevent between five hospital admissions and 27 readmissions per 1000 asthma patients per year. Conclusion: Regular use of low dose inhaled corticosteroids prevents a large proportion of hospital admissions with asthma, both early and later on in the course of the disease.

https://thorax.bmj.com/content/thoraxjnl/57/10/880.full.pdf

Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma.

Inhaled corticosteroids are now recommended as first-line therapy for asthma. Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impact of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids, when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes. Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled cortico-steroids results in a significant reduction in fatalities due to asthma. In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.

Inhaled corticosteroids: impact on asthma morbidity and mortality.

Interleukin-12 (IL-12) and IL-13 are two recently characterized cytokines which play an important role in the induction of T helper cell type 1 (Th1-) and Th2-like cells, respectively. Using the technique of in situ hybridization, we have investigated the expression of these cytokines in bronchial biopsies from nine allergic asthmatics and nine normal control subjects. To determine the effect of steroid therapy on the expression of IL-12 and IL-13 in asthma, the numbers of cells expressing these cytokine mRNA before and after a 1-wk course of oral prednisone in six steroid-sensitive (SS) and five steroid-resistant (SR) moderately severe asthmatics were also examined. There was an increased number of IL-13, and a decreased number of IL-12 mRNA positive cells in asthmatic subjects compared with normal control subjects (p < 0.001). After steroid treatment, the increase in FEV1 values observed in SS asthmatics was accompanied by a significant decrease in cells expressing IL-13 mRNA (p < 0.05) and an increase in the numbers of cells expressing IL-12 mRNA (p < 0.05). In contrast, steroid therapy in SR asthmatics was not associated with significant changes in IL-12 and IL-13 mRNA expression. Thus, allergic asthma is associated with a downregulation of IL-12 mRNA expression and an upregulation of IL-13 mRNA expression. These results suggest an in vivo role for IL-12 and IL-13 in modulating allergic responses and support the notion that the clinical effects of glucocorticoids are at least partially mediated through the modulation of cytokine production.

Pierre Ernst

Papers

Relative Scarcity of Asthma and Atopy among Rural Adolescents Raised on a Farm

Differences in airway remodeling between subjects with severe and moderate asthma.

Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma.

Inhaled corticosteroids: impact on asthma morbidity and mortality.

Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy.