Chronic Obstructive Pulmonary Disease: Research Highlights

January 2014

Chronic obstructive pulmonary disease, or COPD, is a term that covers several conditions, all characterized by persistent blockage of airflow from the lungs and difficulty in breathing. Emphysema, chronic bronchitis and some types of asthma are among the diseases that now fall under the general heading of COPD.

The Global Initiative for Chronic Obstructive Lung Disease has defined COPD as “a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.” (As reported in a paper for the 2013 Cleveland Clinic Pulmonary Hypertension Summit.)

Figures from the World Health Organization suggest that, worldwide, upwards of 50 or 60 million people have been diagnosed with COPD, although such estimates may be low and the number of actual sufferers far greater, given the varying definitions of the condition and evidence that a substantial number of cases go undiagnosed. In the United States, for example, according to the Centers for Disease Control and Prevention, more than 50% of adults with low pulmonary function did not know that they had COPD. The condition is currently the third leading cause of death in the US.

COPD tends to develop slowly and is therefore primarily an affliction of the aged, inordinately affecting those older than 65. Tobacco smoke is a leading cause, along with air pollution from sources both indoor (solid fuels used for heating and cooking) and outdoor. Workplace exposure to chemical fumes or vapors, dusts, and other irritants is another risk factor.

In the US, COPD is more prevalent among people with lower educational and income levels. Worldwide, similarly, up to 90% of deaths from COPD occur in lower- to middle-income nations. Men previously constituted a majority of cases, although, as WHO notes, given increased tobacco use by women in higher-income countries and greater exposure to indoor pollutants in lower-income nations, the incidence in men and women is moving toward parity.

The prevalence of COPD is increasing, as is the burden of health-care costs. In the US alone for the year 2007, the overall cost was estimated at $42 billion. WHO cites an estimate that, in the absence of significant measures to curb tobacco use and other risk factors, total deaths from COPD will increase by more than 30% in the next 10 years. Worldwide, COPD is predicted to account for six million deaths annually.

 

Report: The Latest Pharmaceuticals

At present, there is no cure for COPD. Treatments, such as compounds that dilate air passages to ease breathing, are primarily aimed at relieving symptoms.

Nevertheless, pharmaceutical companies continue to develop new agents and approaches for treating COPD. The latest in a series of “Spotlight On” reports from Thomson Reuters Cortellis Competitive Intelligence examines COPD and the compounds that major pharmaceutical firms are currently marketing or developing.

The infographic below highlights recent efforts to manage and treat COPD, tracking research and patent activity pertaining to inhaled bronchodilator therapies as well as to emergent classes of pharmaceuticals. One of the latter types, p38 kinase inhibitors, is further scrutinized in terms of major patent assignees (with GlaxoSmithKline clearly predominant). By the measure of research papers over the last decade, p38 kinase inhibitors and glucorticoid receptor modulators have occasioned the most activity, although research on mesenchymal stem cells has spiked in recent years, with numbers in 2013 rivaling those for the other two classes.

Download The Future of COPD - infographic

 

Research Highlights

For another snapshot of recent research into COPD, ScienceWatch turned to Thomson Reuters Web of Science. A search on the term “COPD” and its component keywords over the last decade produced some 26,000 papers. The table below lists the 10 most cited.

 

Highly Cited Papers on Chronic Obstructive Pulmonary Disease,
2003-2012

(Listed by citations)

Rank Paper Citations
1 K.F. Rabe, et al., “Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease — GOLD executive summary,” American J. Resp. Crit. Care Med., 176(6): 532-55, 2007. [11 institutions worldwide] 1,941
2 B.R. Celli, et al., “Standards for the diagnosis and treatment of patients with COPD: a summary of the AT/ERS position paper,” European Resp. J., 23(6): 932-46, 2004. [Tufts U. Sch. Med., Boston, MA; U. Edinburgh, UK] 1,555
3 J.C. Hogg, et al., “The nature of small-airway obstruction in chronic obstructive pulmonary disease,” New Engl. J. Med., 350(26): 2645-53, 2004. [U. British Columbia, Vancouver, Canada; Natl. Jewish Res. & Med. Ctr., Denver, CO; U. Pittsburgh, PA] 1,139
4 B.R. Celli, et al., “The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease,” New Engl. J. Med., 350(10): 1005-12, 2004. [7 institutions worldwide] 1,081
5 P.M.A. Calverley, et al., “Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease,” New Engl. J. Med., 356(8): 775-89, 2007. [9 institutions worldwide] 1,038
6 D.P. Tashkin, et al. (UPLIFT Study Investigat.), “A 4-year trial of tiotropium in chronic obstructive pulmonary disease,” New Engl. J. Med., 359(15): 1543-54, 2008. [5 institutions worldwide] 570
7 W.Q. Gan, et al., “Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis,” Thorax, 59(7): 574-80, 2004. [St. Paul’s Hosp., Vancouver, Canada; U. British Columbia, Vancouver, Canada; U. Alberta, Edmonton, Canada] 551
8 P.J. Barnes, S.D. Shapiro, R.A. Pauwels, “Chronic obstructive pulmonary disease: Molecular and cellular mechanisms,” European Resp. J., 22(4): 672-88, 2003. [Imperial Coll. London, UK; Harvard U. Sch. Med., Boston, MA; State U. Ghent, Belgium] 527
9 P. Calverley, et al. (TRISTAN Study Grp.), “Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial,” Lancet, 361(9356): 449-56, 2003. [6 European institutions] 512
10 A.S. Buist, et al. (BOLD Collab. Res. Grp.), “International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study,” Lancet, 370(9589): 741-50, 2007. [12 institutions worldwide] 439
SOURCE: Thomson Reuters Web of Science

Along with general reports on the diagnosis, management, and prevalence of COPD, or on its physiological aspects, a few of the papers examine specific treatments. Paper #6, for example, is a 2008 report on a trial of the bronchodilator tiotropium (now marketed under the brand names Spiriva and Teova). Papers #5 and #9, meanwhile, discuss the combination of two agents: the anti-inflammatory corticosteroid fluticasone, and the beta2-adrenergic receptor agonist salmeterol, a bronchodilator. With its efficacy demonstrated, this combination is now marketed in the US as Advair and under various other names worldwide.

 

Prolific Authors

ScienceWatch also examined the 26,000-papers-plus sampling on COPD to identify notably prolific researchers on the topic over the last decade. These names are listed below.

 

Prolific Researchers on Chronic Obstructive Pulmonary Disease,
2003-2012

(Listed by number of papers in the Web of Science selection on COPD)

Peter J. Barnes
Imperial College London, UK
Emiel F.M. Wouters
Maastricht University, Netherlands
Jørgen Vestbo
University of Manchester, UK, and
University of Southern Denmark, Odense
Jadwiga Wedzicha
University College London, UK
Edwin Silverman
Harvard University, Cambridge, MA USA
Marc Decramer
KU Leuven, Belgium
Don D. Sin
University of British Columbia, Vancouver, Canada
Marc Miravitlles
University Hospital Vall d’Hebron, Barcelona, Spain
Michael Polkey
Imperial College London, UK
Peter Calverley
Aintree University Hospital, Liverpool, UK
SOURCE: Thomson Reuters Web of Science

Atop the list, having coauthored more than 200 of the selected papers on COPD since 2003, is Peter J. Barnes of Imperial College London. Joining Barnes on the list is another Imperial College researcher, Michael Polkey, who contributed to more than 130 papers.

Barnes appears on two of the featured 10 top-cited papers in the table (#1, #8), as does Peter Calverley (#2, #5), while other names on the list each contributed to one of the blockbusters: Jorgen Vestbo (#2), Marc Decramer (#6), and Don Sin (#7).

Overall, among the authors, UK-based researchers make a strong showing, occupying five of the 10 slots, with Europe accounting for three of the names, and North America two.

Many of the researchers on the list—Barnes, Vestbo, Decramer, and Calverley, along with Emiel Wouters and Marc Miravitlles—were previously featured by ScienceWatch, in a Special Topic devoted to COPD in 2010, based on a slightly earlier selection of literature. In extended interviews, Barnes, Vestbo, and Calverley discuss their work, and the Special Topic presentation includes listings of highly cited institutions, journals, and nations in COPD research.

For the present survey, ScienceWatch also identified institutions that produced the highest quantities of reports devoted to COPD.

 

Prolific Institutions in Chronic Obstructive Pulmonary Disease,
2003-2012

(Listed by number of papers in the Web of Science selection on COPD)

Harvard University, Cambridge, MA USA
Imperial College London, UK
University of British Columbia, Vancouver, Canada
Brigham and Women’s Hospital, Boston, MA USA
University of Pittsburgh, PA USA
University of Toronto, Canada
University of California, Los Angeles USA
University of Groningen, Netherlands
McGill University, Montreal, Canada
Johns Hopkins University, Baltimore, MD USA
SOURCE: Thomson Reuters Web of Science

Harvard University and Imperial College London stand atop the list (and very close together, having both accounted for roughly 560 of the papers in the 2003-2012 Web of Science selection). The University of British Columbia exceeded 400 papers, while Johns Hopkins came in with just over 250.

As with the list of researchers, European and North American institutions predominate. In fact, in the extended Web of Science listings of prolific agencies, one must read well down the display to arrive at the first Asia-based entity, Kyoto University, Japan, with just over 90 papers. This suggests that, at least in the present sample of papers, COPD’s worldwide prevalence as a research priority does not yet match its growing global burden.

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.