Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019.

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

Seasonal and Regional Variations in Chronic Obstructive Pulmonary Disease Exacerbation Rates in Adults without Cardiovascular Risk Factors.

RATIONALE: Colder temperatures have been shown to increase hospitalization and mortality rates in adults with chronic obstructive pulmonary disease (COPD) and cardiac disease. Seasonal influences on exacerbation rates in adults with severe COPD but without significant cardiovascular disease are unclear. In addition, regional variations in COPD exacerbations in North America have not yet been explored. OBJECTIVES: In this study, we sought to determine the seasonal and regional variability in exacerbation rates in those with COPD but without significant cardiovascular risk factors. METHODS: We studied adults without cardiovascular risk factors from STATCOPE (Simvastatin in the Prevention of COPD Exacerbations) and placebo arm of MACRO (Azithromycin for the Prevention of Exacerbations of COPD) studies. Forty-five study sites were divided into climate regions in Canada and the United States; seasons were defined as winter, spring, summer, and fall. The primary outcome was the rate of COPD exacerbation. Secondary outcomes included time to first exacerbation, severity of exacerbations, all-cause mortality, and antibiotic and steroid use. RESULTS: We analyzed 1,175 subjects with a mean age of 63.3 ± 8.6 years, forced expiratory volume in 1 second of 41.5 ± 17.1% predicted, and 53.6 ± 29.4 pack-years of smoking history. The COPD exacerbation rate was higher in winter (0.13 exacerbations/person-month) than in spring, summer, and fall (0.11, 0.079, and 0.10 exacerbations/person-month, respectively) (P < 0.001). Summer had the highest proportion of severe exacerbations (40.5%) compared with spring, fall, and winter (32.6%, 34.7%, and 33.1%, respectively) (P = 0.004). Mortality was highest in spring and winter (34% and 30%, respectively). There was significant regional variability in the time to first exacerbation, with the Southeast and West having longer median times to first exacerbation (350 and 342 d, respectively, compared with 184 d in other regions) (P < 0.001). CONCLUSIONS: Significant seasonal and regional variability exist in the rate and severity of exacerbations and overall mortality in adults with COPD without cardiovascular disease.

SNP rs3088308 is a risk factor for poor lung function in healthy smokers.

OBJECTIVE: To see if single nucleotide polymorphisms of pulmonary innate immune molecule surfactant protein D were associated with poor lung function in smokers. METHODS: The study was conducted at Shaikh Zayed Hospital, Lahore, Pakistan, from April 2008 to August 2010, and comprised relatives and attendants of patients, as well as college and university students. Self-reported healthy smokers who demonstrated no airflow obstruction on spirometry were included. Deoxyribonucleic acid was extracted from their blood sample and genotyped for single nucleotide polymorphisms rs721917 and rs3088308 by polymerase chain reaction and restriction analysis. Serum was separated for measurement of surfactant protein D levels by a commercially available enzyme-linked immunosorbent assay based kit. Lung functions were compared between subjects possessing major and minor alleles using two-tailed Student's t-test. Multiple linear regression analysis was conducted to analyse the effect of age, smoking and the two single nucleotide polymorphisms on forced expiratory volume in 1 second. RESULTS: Of the 122 participants, all of whom were men, 98(80.33%) were smokers while 24(19.67%) had never smoked. Of the former, 90(91.84%) were current smokers and 8(8.16%) were ex-smokers. The overall mean age was 35.8±10.9 years. The mean surfactant protein D level was 121.4±61.6ng/ml. In case of rs3088308, all lung function variables were reduced in patients with a minor allele and the results for forced expiratory volume in 1 second (p=0.016), forced expiratory volume in 1 second (%) predicted (p=0.009), forced vital capacity (p=0.048) and forced vital capacity (%) predicted (p=0.048) were statistically significant. Age had the highest influence on lung function (p<0.001) followed by smoking status (p=0.04) and single nucleotide polymorphisms rs3088308 minor allele (p=0.04). CONCLUSIONS: Single nucleotide polymorphisms rs3088308 was found to modulate serum surfactant protein D levels and may be a risk factor for development of chronic obstructive pulmonary disease among smokers.

Predictors of pulmonary hypertension on high-resolution computed tomography of the chest in systemic sclerosis: a retrospective analysis.

PURPOSE: To evaluate the imaging features on high-resolution computed tomography (HRCT) of the chest and the clinical parameters that are associated with pulmonary hypertension in systemic sclerosis. We specifically investigated whether main pulmonary artery (MPA) diameter and burden of lung fibrosis are predictors of pulmonary hypertension in these patients. METHODS: We retrospectively retrieved the database information of patients with systemic sclerosis seen at our hospital between January 2007 and December 2008. A total of 75 patients had HRCT of the chest, pulmonary function testing (PFT), and echocardiography within 6 months of each other. The echocardiography images were reviewed by a level-3 echocardiographer, and 29 cases were excluded because of suboptimal evaluation of pulmonary artery (PA) pressure. Peak PA pressures and PFT of the remaining 46 cases (43 women and 3 men) were charted. The PFT included total lung capacity (TLC), diffusion capacity of lung for carbon monooxide (DLCO) and the ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC). The HRCT of the chest of each patient was read by a chest radiologist. The extent of ground glass, reticulation, and honeycombing was objectively scored. The maximum diameter of the main pulmonary artery (MPAD) and ascending aorta were measured. The ratio of main pulmonary artery diameter and ascending aortic diameter (MPAD/AD) and ratio of main pulmonary artery diameter and body surface area (MPAD/BSA) were also calculated. RESULTS: Statistical analysis done by using a multivariate model showed that the calculated fibrotic score strongly correlated with peak PA pressures (P < .001). MPAD (P = .0175), and the ratio MPAD/AD (P = .0102) also showed a statistically significant correlation with peak PA pressures. By using stepwise regression analysis, the fibrotic score was found to be the most reliable independent predictor of pulmonary hypertension. CONCLUSION: HRCT-determined severity and extent of pulmonary fibrosis may be helpful in screening for pulmonary hypertension in patients with systemic sclerosis.

The sex factor: epidemiology and management of chronic obstructive pulmonary disease in British Columbia.

BACKGROUND: The prevalence and mortality of chronic obstructive pulmonary disease (COPD) in women have been predicted to overtake that of men within the next decade. These predictions are based in part on data from surveys using self-reports of a COPD diagnosis. Whether these predictions have been realized is unknown. METHODS: The prevalence and mortality of men and women in British Columbia were compared from fiscal years 1992/1993 to 2003/2004 using administrative health services data. Case definitions for COPD were developed using International Classification of Diseases ninth and 10th revision (ICD-9/10) codes applied to medical and hospital data. Individuals 45 years and older, who had at least two physician visits or one hospitalization for specified COPD ICD-9/10 codes within a 365-day window, were considered to be cases. Cases were ascertained from 1992 to 2004. RESULTS: In 2003/2004, men had a greater prevalence (4.7% versus 4.0% in women) and a higher all-cause mortality rate (5.4% versus 4.1% in women) than women. Both men and women with COPD had low COPD medication use (45%) and low referral for lung function testing (55%). Including the ICD-9 code for 'bronchitis, not specified as acute or chronic' (ICD-9 490) in the case definition resulted in a greater prevalence of COPD in women than in men overall, and in the 45 to 64 year age group. CONCLUSION: Prevalence and mortality measured with administrative health data do not show evidence of relative increase in the prevalence of COPD for women in British Columbia. However, further analysis of ICD-9 490 may identify an early 'at-risk' group, specifically in women.

Sex differences in severe pulmonary emphysema.

RATIONALE: Limited data on sex differences in advanced COPD are available. OBJECTIVES: To compare male and female emphysema patients with severe disease. METHODS: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. MEASUREMENTS AND MAIN RESULTS: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. CONCLUSIONS: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.

Cost-effectiveness of inhaled corticosteroids for chronic obstructive pulmonary disease according to disease severity.

PURPOSE: Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), but their cost-effectiveness is not known. METHODS: We used a Markov model to determine, from a societal perspective, the cost-effectiveness of four treatment strategies involving inhaled corticosteroids: no use regardless of COPD severity; use in all disease stages; use in patients with stage 2 or 3 disease (forced expiratory volume in 1 second [FEV(1)] <50% of predicted); and use in patients with stage 3 disease (FEV(1) <35% of predicted). Data from the literature were used to estimate mortality, exacerbation, and disease progression rates, as well as the costs associated with care and quality-adjusted life-years (QALYs), according to disease stage and use or nonuse of inhaled corticosteroids. A time horizon of 3 years was used. RESULTS: Use of inhaled corticosteroids in patients with stage 2 or 3 disease was associated with a cost of 17,000 dollars per QALY gained. In stage 3 patients, use resulted in a cost of 11,100 dollars per QALY gained. Providing inhaled corticosteroids to all COPD patients was associated with a less favorable cost-effectiveness ratio. Results were robust to various assumptions in a Monte Carlo simulation. CONCLUSION: In patients with COPD, use of inhaled corticosteroids in those with stage 2 or 3 disease for 3 years results in improved quality-adjusted life expectancy at a cost that is similar to that of other therapies commonly used in clinical practice.