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.

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.

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Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary

The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype.

The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

Objectives  To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design  Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources  Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection  Randomised, double blind, placebo controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results  25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity Conclusions  Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration  PROSPERO CRD42014013953.

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Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Vitamin D: modulator of the immune system.

BACKGROUND Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. DESIGN Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) SETTING University Hospitals Leuven, Leuven, Belgium. PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations. INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. MEASUREMENTS The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). LIMITATION This was a single-center study with a small sample size. CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. PRIMARY FUNDING SOURCE Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

Low serum vitamin D levels have been associated with inflammation and infection and occur in many patients with severe chronic obstructive pulmonary disease (COPD). This randomized trial assigned 1...

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High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease

Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system

Chronic kidney disease (CKD) is characterized by a loss of kidney function and dysregulation of vitamin D metabolism. Well known are the defects in final activation of vitamin D to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], resulting in renal osteodystrophy. However, in recent years, 1,25(OH)2D3 has been identified as having effects far beyond calcium and bone metabolism. In this review, specific attention is given to the effects of 1,25(OH)2D3 on the immune system and the implications of vitamin D deficiency, a feature of many patients with CKD, on immune function.

Femke Baeke

Papers

Vitamin D: modulator of the immune system.

High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease

Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system

Vitamin D insufficiency: implications for the immune system