It is estimated that the world population will reach a record 7.3 billion in 2015, and the high burden of chronic conditions associated with ageing and smoking will increase further. Respiratory diseases in general receive little attention and funding in comparison with other major causes of global morbidity and mortality.In particular, chronic obstructive pulmonary disease (COPD) has been a major public health problem and will remain a challenge for clinicians within the 21st century. Worldwide, COPD is in the spotlight, since its high prevalence, morbidity and mortality create formidable challenges for health-care systems. This review emphasizes the magnitude of the COPD problem from a clinician's standpoint by drawing extensively from the new findings of the Global Burden of Disease study. Updated,distilled information on the population distribution of COPD is useful for the clinician to help provide an appreciation of the relative impact of COPD in daily practice compared with other chronic conditions, and to allocate minimum resources in anticipation of future needs in care. Despite recent trends in reduction of COPD standardized mortality rates and some recent successes in anti-smoking efforts in a number of Western countries, the overarching demographic impact of ageing in an ever-expanding world population, joined with other factors such as high rates of smoking and air pollution in Asia, will ensure that COPD will continue to pose an ever-increasing problem well into the 21st century.

Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we measured cytokines produced by human AM exposed to ambient particles of different composition and size. Identified cytokines were also measured in the circulation of healthy young subjects exposed to air pollutants during the 1997 Southeast Asian forest fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert carbon particles, and latex particles of different sizes (0.1, 1, and 10 microm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbon (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximum TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212%, p < 0.05) showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 microg/ml (812 +/- 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alpha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM(10) during an episode of acute air pollution. These results show that a range of different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We postulate that these cytokines induced a systemic response that has an important role in the pathogenesis of the cardiopulmonary adverse health effects associated with atmospheric pollution.

Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline.

Atmospheric pollution increases cardiopulmonary morbidity and mortality by unexplained mechanisms. Phagocytosis of fine particles (PM(10)) by rabbit alveolar macrophages elevates white blood cells (WBC) by releasing precursors from the bone marrow and this could contribute to the pathogenesis of cardiopulmonary disease. The present study examined the association between acute air pollution caused by biomass burning and peripheral WBC counts in humans. Serial measurements of the WBC count made during the 1997 Southeast Asian Smoke-haze (Sep 29, Oct 27) were compared with a period after the haze cleared (Nov 21, Dec 5) using peripheral blood PMN band cells to monitor marrow release. The results showed that indices of atmospheric pollution were significantly associated with elevated band neutrophil counts expressed as a percentage of total polymorphonuclear leukocytes (PMN), with maximal association on zero and 1 lag day for PM(10) and 3, and 4 lag days for SO(2) (p value < 0.000). We conclude that atmospheric pollution caused by biomass burning is associated with elevated circulating band cell counts in humans because of the increased release of PMN precursors from the marrow. We speculate that this response contributes to the pathogenesis of the cardiorespiratory morbidity associated with acute air pollution.

Background: People with known risk factors for chronic obstructive pulmonary disease (COPD) are important targets for screening and early intervention. We sought to measure the prevalence of COPD among such individuals visiting a primary care practitioner for any reason. We also evaluated the accuracy of prior diagnosis or nondiagnosis of COPD and identified associated clinical characteristics. Methods:We recruited patients from three primary care sites who were 40 years or older and had a smoking history of at least 20 pack-years. Participants were asked about respiratory symptoms and underwent postbronchodilator spirometry. COPD was defined as a ratio of forced expiratory volume in the first second of expiration to forced vital capacity (FEV 1 /FVC) of less than 0.7 and an FEV 1 of less than 80% predicted. Results:Of the 1459 patients who met the study criteria, 1003 (68.7%) completed spirometry testing. Of these, 208 were found to have COPD, for a prevalence of 20.7% (95% confidence interval 18.3%-23.4%). Of the 205 participants with COPD who completed the interview about respiratory symptoms before spirometry, only 67 (32.7%) were aware of their diagnosis before the study. Compared with patients in whom COPD had been correctly diagnosed before the study, those in whom COPD had been overdiagnosed or undiagnosed were similar in terms of age, sex, current smoking status and number of visits to a primary care practitioner be cause of a respiratory problem.Interpretation: Among adult patients visiting a primary care practitioner, as many as one in five with known risk factors met spirometric criteria for COPD. Underdiagnosis of COPD was frequent, which suggests a need for greater screening of at-risk individuals. Knowledge of the prevalence of COPD will help plan strategies for disease management. AbstractPreviously published at www.cmaj.ca

BackgroundChronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).MethodsNational COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.ResultsNational COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.ConclusionsSmoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries.

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, crosssectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high-and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1. 42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. @ERSpublications Tuberculosis should be considered a potentially important risk factor for obstructive disease and low lung function

Rationale: COPD is associated with reduced life expectancy. Objectives: To determine the association between small airway pathology and long-term survival after lung volume reduction in chronic obstructive pulmonary disease (COPD) and the effect of corticosteroids on this pathology. Methods: Patients with severe (GOLD-3) and very severe (GOLD-4) COPD (n 5 101) were studied after lung volume reduction surgery.Respiratory symptoms, quality of life, pulmonary function, exercise tolerance, chest radiology, and corticosteroid treatment status were assessed preoperatively. The severity of luminal occlusion, wall thickening, and the presence of small airways containing lymphoid follicles were determined in resected lung tissue. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the relationship between survival and small airway pathology. The effect of corticosteroids on this pathology was assessed by comparing treated and untreated groups. Measurements and Main Results: The quartile of subjects with the greatest luminal occlusion, adjusted for covariates, died earlier than subjects who had the least occlusion (hazard ratio, 3.28; 95% confidence interval, 1.55-6.92; P 5 0.002). There was a trend toward a reduction in the number of airways containing lymphoid follicles (P 5 0.051) in those receiving corticosteroids, with a statistically significant difference between the control and oral 6 inhaled corticosteroid-treated groups (P 5 0.019). However, corticosteroid treatment had no effect on airway wall thickening or luminal occlusion. Conclusions: Occlusion of the small airways by inflammatory exudates containing mucus is associated with early death in patients with severe emphysema treated by lung volume reduction surgery. Corticosteroid treatment dampens the host immune response in these airways by reducing lymphoid follicles without changing wall thickening and luminal occlusion.Keywords: premature death in COPD; airway remodeling; mucosal immune response; corticosteroidsThe emphysematous destruction of the lung's gas-exchanging surface and obstruction to flow in the small conducting airways are responsible for the irreversible airflow limitation that defines chronic obstructive pulmonary disease (COPD) (1). We previously reported a negative association between the severity of the pathology in the small conducting airways and FEV 1 over the full range of COPD severity (2). The primary objective of the present study was to test the hypothesis that this pathology might influence survival of patients in a 72-month follow-up period after lung volume reduction surgery (LVRS) (3, 4). A secondary objective was to determine if corticosteroid therapy had any influence on small airway pathology that might provide insight into the recent report that long-term steroid therapy reduces exacerbations of COPD but increases the incidence of pneumonia (5). Preliminary reports on the data contained in this article have been presented in abstract form at the Aspen Lung Conference (6) and at annual m...