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.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Global strategy for asthma management and prevention

ALAT
: alanine aminotransferase
ASAT
: aspartate aminotransferase
APAH
: associated pulmonary arterial hypertension
BAS
: balloon atrial septostomy
BMPR2
: bone morphogenetic protein receptor 2
BNP
: brain natriuretic peptide
BPA
: balloon pulmonary angioplasty
BREATHE
: Bosentan

/pdf/2015-esc-ers-guidelines-for-the-diagnosis-and-treatment-of-y26yabnnom.pdf

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma

Introduction and objectives National Institute for Health and Care Excellence (NICE) recommends long–acting bronchodilators, including β2-agonists (LABAs) or muscarinic antagonists (LAMAs) as first line maintenance treatment for patients with COPD. The aim of this descriptive study was to characterise a cohort of COPD patients who were on maintenance bronchodilator monotherapy for at least six months to establish their disease burden, measured by healthcare utilisation. Methods Data were extracted from the UK Clinical Practice Research Datalink (CPRD) which also linked to Hospital Episode Statistics (HES). The monotherapy period spanned the first prescription of a LABA or LAMA until the end of the study period (31/12/2013) or until step-up to dual/triple therapy; for example the addition of another long acting bronchodilator, an ICS or ICS/LABA. A minimum of four consecutive prescriptions and six months on continuous monotherapy were required for study entry. Patients Results A cohort of 8,811 COPD patients (94% GOLD stage A or B) on maintenance monotherapy was identified between 2002 and 2013; 45% (N=3,947) of these patients were still on monotherapy by the end of the study period. The median time from first COPD diagnosis to first monotherapy prescription was 56 days while the median time on maintenance bronchodilator monotherapy was 748 days. The median number of prescriptions during this period was 14. Patients had a median of 19 HCP consultations and a mean of 0.1 (95% CI 0.1, 0.2, N= 8,811) COPD exacerbations and 0.02 (95% CI 0.01, 0.02, N=4,848) COPD hospitalisations per year. Conclusion In summary, COPD patients who are on maintenance bronchodilator monotherapy for at least six months appear to remain on this therapy for over two years despite having a disease burden that requires healthcare resources, particularly HCP consultations, at a cost to the NHS.

https://thorax.bmj.com/content/thoraxjnl/69/Suppl_2/A186.1.full.pdf

P248 Current Copd Disease Burden Associated With Maintenance Monotherapy In The Uk

I read with interest the recent article by Meijer and colleagues on the effects of inhaled fluticasone and prednisolone on clinical and inflammatory parameters in patients with asthma.1 Rather than focusing on the differences between oral and inhaled corticosteroid, I believe that a more important finding is the effect of a fourfold increase in the dose of fluticasone on the therapeutic ratio. For airway parameters there were no significant differences in the effects on bronchial hyperresponsiveness to methacholine and adenosine monophosphate or on sputum eosinophils between fluticasone in doses of 500 μg and 2000 μg per day. However, for systemic bioactivity markers there were significant differences between the two doses of fluticasone on serum cortisol levels and blood eosinophils. Taken together these findings suggest that, at least for effects on airway hyperresponsiveness and inflammation, the therapeutic ratio for fluticasone declines sharply above a watershed dose of 500 μg per day. This result is perhaps not surprising, given the high glucocorticoid topical potency for in vitro anti-inflammatory activity with fluticasone.2 

It is also important to point out that the study by Meijer et al was performed using fluticasone delivered via a Diskhaler dry powder inhaler device, which delivers a twofold lower respirable fine particle dose than a fluticasone propionate pressurised metered dose inhaler.3 This is due to the larger particle size from the fluticasone dry powder inhaler. Hence, increasing the nominal dose of fluticasone dry powder may result in a proportionately greater …

https://thorax.bmj.com/content/thoraxjnl/55/3/251.2.full.pdf

Therapeutic ratio of inhaled fluticasone

Bronchoprotective tolerance with inhaled corticosteroid/long-acting β-agonist treatment.

Garcia-Arieta [1] interprets our data [2] purely from a regulatory perspective with regard to demonstrating equivalence. In this regard, we demonstrated a significant overall dose–response relation from regression analysis of the common slope for shift in methacholine PC20, indicating assay sensitivity for this outcome. However, when one inspects the difference in PC20 shift between the 200 and 800 µg doses, while there was significant dose separation it has to be taken in the context of the biological variability which is of the order of ±1 doubling dilution (i.e. ±2-fold shift). Thus, one needs to distinguish between a statistically significant difference from what may be clinically irrelevant. Pointedly, our patients were selected a priori for being methacholine responsive, with a mean PC20 of 0.66 mg/ml−1, i.e. they had plenty of room for improvement in response to inhaled corticosteroid. When comparing the formulations at each dose level, the confidence limits for the mean difference in PC20 was contained within accepted limits of variability of ±1 doubling dilution, indicating therapeutic equivalence. Our study shows that even using n = 89 patients, while the point estimate for relative potency was close to unity, the 95% confidence interval was well outside of accepted pharmacodynamic equivalence limits. Given that this was performed within a single centre with considerable experience of challenge studies, we are of the firm opinion that it is not feasible to assess relative potency using Finney, and as such this should no longer be recommended in current guidelines for establishing equivalence. Although we also showed significant dose separation for suppression of exhaled nitric oxide, the mean difference between 200 and 800 µg was rather small, amounting to 14% with HFA and 11% with CFC, in comparison to 29 and 20% differences, respectively, for methacholine PC20 shift.

We evaluated pharmacokinetic outcomes at steady state to mirror what happens in real-life clinical practice, where patients take their inhaled steroid twice daily and not as single doses, i.e. also to reflect the chronic dosing protocol for our challenge study. In fact, our data for area under the curve showed that the two formulations were equivalent within conventional limits of ±20%, in keeping with the challenge data when comparing the methacholine PC20 shift at each dose. Finally, subtle differences in pharmacokinetic and pharmacodynamic outcomes pointed out by Garcia-Arieta [1] need to be put in their true perspective, because variations in real-life inhaler technique will result in at least 50% differences in dose delivered to the lungs, even within the same individual from day to day. Thus, from a clinical perspective, a 10% difference in delivered dose is rather meaningless for the patient. In the light of our study, we believe that the guidelines are no longer in touch with the reality of performing clinical trials using surrogate inflammatory end-points with inhaled steroids and especially the need to calculate relative potency ratios using Finney.

/pdf/guidelines-to-establish-relative-potency-are-not-in-touch-ht4xmdobfw.pdf

Guidelines to establish relative potency are not in touch with reality

Observational Data With Inhaled Corticosteroid/Long-Acting Beta-Agonist/Long-Acting Muscarinic Antagonist May Not Reflect Current Practice With Single Triple Inhalers

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