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.

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Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

We nonetheless take the opportunity to remark on this point that there is no high-level evidence of which vitamin D metabolites are safer and faster in normalizing sHPTH, and more importantly, the optimal dose of vitamin D3 capable of normalizing rapidly sHPTH is still being discussed and has not been established. In addition, a number of studies have demonstrated that the commonly used doses of vitamin D ( 800 UI daily), also suggested by the drug industry, may fail to normalize PTH levels in older adults with sHPTH. 8,9 The choice of calcitriol in the experimental design of our study was based mainly on the need to use a treatment that could rapidly resolve sHPTH and on the lack of available preparation of vitamin D3 at high concentrations in Italy at the time of the study.In conclusion, although we agree with the statement that plain vitamin D is the treatment of choice for vitamin D deficiency, we disagree with the interpretation of the manuscript given by Dr. Vieth, because the goal of identifying a treatment of choice for sHPTH was outside the scope of our study, whose most relevant outcome consists instead of the observation that persistence of sHPTH reduces BMD response to alendronate. To respond to the issue raised by Dr. Vieth, RCTs are needed to assess the vitamin D metabolite of choice in normalizing PTH.

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor–deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.