Elsevier

The Lancet

Volume 378, Issue 9795, 10–16 September 2011, Pages 1038-1047
The Lancet

Series
Controversies in treatment of chronic obstructive pulmonary disease

https://doi.org/10.1016/S0140-6736(11)61295-6Get rights and content

Summary

Chronic obstructive pulmonary disease (COPD) is a chronic disorder with substantial comorbidity and major effects attributable to the high morbidity and mortality rates. Despite an increasing evidence base, some important controversies in COPD management still exist. The classic way to define COPD has been based on spirometric criteria, but more relevant diagnostic methods are needed that can be used to describe COPD severity and comorbidity. Initiation of interventions earlier in the natural history of the disease to slow disease progression is debatable, there are many controversies about the role of inhaled corticosteroids in the management of COPD, and long-term antibiotics for prevention of exacerbation have had a resurgence in interest. Novel therapeutic drugs are urgently needed for optimum management of the acute COPD exacerbation. COPD is a complex disease and consists of several clinically relevant phenotypes that in future will guide its management.

Introduction

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disorder that affects millions of people worldwide. It has a major societal effect due to the high morbidity and mortality rates.1, 2 The main risk factors for the disease include cigarette smoke in most developed countries, but indoor air pollution, biomass fuel, and occupational exposures are increasingly recognised as major risk factors. Notably, knowledge about the immunological and pathological processes implicated in COPD are almost exclusively based on disease caused by cigarette smoke.3 Therefore, effective treatments are needed for non-smoking patients with COPD because these individuals are regularly excluded from clinical trials.

Patients with COPD frequently have comorbidities because smoking is a general risk factor for a range of other chronic illnesses such as cardiovascular disease and lung cancer, also peaking in prevalence in the fifth to sixth decades. Not only is COPD a heterogeneous disease with varying disease activity, but other comorbid illnesses might be major determinants of disease severity. The current focus on lung function impairment as the main or sole determinant of disease classification is no longer feasible for estimation of risk and prognosis. New treatment algorithms will need to be developed on the basis of our current understanding of COPD as a complex disorder that not only affects the lungs.4

Globally, the management of chronic non-communicable diseases, including COPD, is likely to become more complex in the rapidly ageing population. Health-care systems are increasingly challenged to offer affordable, humane care models, based on best current evidence. Treatment recommendations and guidelines rely on reported evidence. However, the systematic exclusion of patients from large clinical trials of COPD on the basis of complex comorbidities and age is one of the main obstacles in the generation of universally acceptable guidance for treatment. The participation of a broad range of medical specialties, and patient organisations, is needed to address the controversial issues before treatment guidelines can be drawn up. Here, we discuss the controversies in the treatment of COPD.

Section snippets

What defines disease severity?

The conceptual view of COPD has changed from a rather simplistic view of a cigarette-smoke-induced illness involving chronic bronchitis and varying degrees of lung emphysema to a complex disorder affecting patients’ lives on several levels. Previous attempts to classify the severity of the disease by spirometric methods such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification were logical, but the different classes of severity were chosen on the basis of expert

Should treatment be started early?

Data from the observational ECLIPSE study11 showed that 22% of patients with GOLD stage 2 (FEV1 50–79% predicted) moderate COPD already had frequent exacerbations (figure 1) and were thus at risk of rapid decline in FEV1, poor health status, hospital admission, and increased mortality rate.12, 13, 14 Severe disease was targeted in most interventional studies of symptomatic (bronchodilators) or anti-inflammatory treatments; therefore, little evidence exists for the benefit of therapy in early

When should inhaled corticosteroids be prescribed?

Inhaled corticosteroids are the main anti-inflammatory treatment for patients with asthma. They alone or in combination with longacting bronchodilator drugs are also used extensively in COPD, yet the airway inflammatory response is different in the two disorders, with a preponderance of CD8 lymphocytes and neutrophils in the airways of patients with COPD that are related to disease severity.30 Anti-inflammatory effects of inhaled corticosteroids in COPD and asthma were compared in only a few

Should treatment focus on cardiac comorbidities?

Because of the frequency of chronic comorbidities in patients with COPD54 and their effect on patient outcomes, including acute exacerbations,55, 56 a more comprehensive approach to COPD treatment might focus on these targets to modify the natural course of the disease.57, 58 This focus is particularly relevant for common comorbid disorders that seem more preventable and treatable than is COPD, such as cardiovascular and metabolic disorders. The available evidence seems to be increasingly in

What is the role of long-term antibiotics?

Although healthy people with normal lung function and without a history of smoking were thought to have a sterile lower respiratory tract, data suggest that the lungs have a bacterial microbiome that is diverse but different from that in the oral cavity and nasopharynx (figure 2).72, 73 In patients with COPD, there is evidence of the presence of airway bacteria in the lower airway in up to 50% of patients in the stable state by use of traditional bacterial culture techniques.74, 75, 76 Lower

How effective is management of acute exacerbations?

COPD exacerbations have an important effect on health status, disease progression, and mortality rate.85 An important goal of treatment of the acute exacerbation is to prevent hospital admission and reduce health-care costs. Patients often present late in the time course of the exacerbation and some evidence suggests that delayed treatment of exacerbation leads to longer exacerbations and hospital admission.86 Thus, a key objective of COPD management programmes must be early recognition of

Phenotypes of COPD and therapeutic consequences

The usefulness of conventional methods for the diagnosis, assessment, and management of COPD are debatable.101 The disease is defined by the presence of airflow limitation that is not fully reversible, and treatment is mostly guided by the severity of this limitation.45 COPD, however, is a complex disease, with a range of pulmonary and extrapulmonary components, and significant heterogeneity with respect to clinical presentation, physiology, imaging, response to treatment, decline in lung

Search strategy and selection criteria

We searched PubMed with the search terms “COPD”, “phenotype”, “exacerbations”, “inhaled corticosteroids”, “inhaled bronchodilators”, “co-morbidity”, and “long-term antibiotics” for papers published up to 2011. There were no language restrictions. We also searched reference lists identified in articles that were found in the searches. Clinical practice guidelines were also included.

References (104)

  • GB Mancini et al.

    Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease

    J Am Coll Cardiol

    (2006)
  • V Khurana et al.

    Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans

    Chest

    (2007)
  • PM Ridker et al.

    Baseline characteristics of participants in the Jupiter trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity c-reactive protein

    Am J Cardiol

    (2007)
  • SR Salpeter et al.

    Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis

    Respir Med

    (2003)
  • ME Tinetti et al.

    The end of the disease era

    Am J Med

    (2004)
  • AT Hill et al.

    Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis

    Am J Med

    (2000)
  • RA Stockley et al.

    Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD

    Chest

    (2000)
  • JA Wedzicha et al.

    COPD exacerbations: defining their cause and prevention

    Lancet

    (2007)
  • L Davies et al.

    Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial

    Lancet

    (1999)
  • Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach

  • JC Hogg et al.

    The nature of small-airway obstruction in chronic obstructive pulmonary disease

    N Engl J Med

    (2004)
  • DM Mannino et al.

    Interpreting lung function data using 80% predicted and fixed thresholds identifies patients at increased risk of mortality

    Chest

    (2011)
  • PW Jones et al.

    Development and first validation of the COPD assessment test

    Eur Respir J

    (2009)
  • BR Celli et al.

    The body-mass index, airflow obstruction, dyspnea and exercise capacity index in chronic obstructive pulmonary disease

    N Engl J Med

    (2004)
  • M Cazzola et al.

    Outcomes for COPD pharmacological trials: from lung function to biomarkers

    Eur Respir J

    (2008)
  • JR Hurst et al.

    Susceptibility to exacerbation in chronic obstructive pulmonary disease

    N Engl J Med

    (2010)
  • GC Donaldson et al.

    The relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease

    Thorax

    (2002)
  • TAR Seemungal et al.

    Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (1998)
  • JJ Soler-Cataluna et al.

    Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    Thorax

    (2005)
  • AK Johnston et al.

    Relationship between lung function impairment and incidence or recurrence of cardiovascular events in a middle-aged cohort

    Thorax

    (2008)
  • JR Feary et al.

    Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care

    Thorax

    (2010)
  • M Decramer et al.

    Treatment of COPD: the sooner the better?

    Thorax

    (2010)
  • P-O Bridevaux et al.

    Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD

    Thorax

    (2008)
  • D Ofir et al.

    Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I COPD

    Am J Respir Crit Care Med

    (2008)
  • DE O'Donnell et al.

    Evaluation of acute bronchodilator reversibility in patients with symptoms of GOLD stage I COPD

    Thorax

    (2009)
  • G Johansson et al.

    Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD

    Prim Care Respir J

    (2008)
  • PM Calverley et al.

    Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease

    N Engl J Med

    (2007)
  • DP Tashkin et al.

    A 4-year trial of tiotropium in chronic obstructive pulmonary disease

    N Engl J Med

    (2008)
  • CR Jenkins et al.

    Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study

    Respir Res

    (2009)
  • T Troosters et al.

    Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT trial

    Eur Respir J

    (2010)
  • C Vogelmeier et al.

    Tiotropium versus salmeterol for the prevention of COPD exacerbations

    N Engl J Med

    (2011)
  • J Bourbeau et al.

    Patient adherence in COPD

    Thorax

    (2008)
  • J Vestbo et al.

    Adherence to inhaled therapy, mortality and hospital admission in COPD

    Thorax

    (2009)
  • T O'Shaughnessy et al.

    Inflammation in bronchial biopsies of subjects with chronic bronchitits: inverse relationship of CD8+ T lymphocytes with FEV1

    Am J Respir Crit Care Med

    (1997)
  • KL Hattotuwa et al.

    The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind placebo-controlled biopsy study

    Am J Respir Crit Care Med

    (2002)
  • TS Lapperre et al.

    Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease

    Ann Intern Med

    (2009)
  • NC Barnes et al.

    Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease

    Am J Respir Crit Care Med

    (2006)
  • J Bourbeau et al.

    Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a randomised controlled trial

    Thorax

    (2007)
  • NR Anthonisen et al.

    Smoking and lung function of Lung Health Study participants after 11 years

    Am J Respir Crit Care Med

    (2002)
  • Continuous or nocturnal oxygen therapy in hypoxaemic chronic obstructive lung disease

    Ann Intern Med

    (1980)
  • Cited by (60)

    • Understanding COPD: A vision on phenotypes, comorbidities and treatment approach

      2016, Revista Portuguesa de Pneumologia (English Edition)
    • COPD: A stepwise or a hit hard approach?

      2016, Revista Portuguesa de Pneumologia (English Edition)
      Citation Excerpt :

      Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, mainly because patient stratification is not consensual across guidelines.1–5 Although there are some undisputed recommendations, such as smoking cessation, physical activity programs, and influenza and pneumococcal vaccination, there is still debate regarding the management of COPD.6–12 The therapeutic approach proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and based solely on the GOLD classification of COPD,2 is not entirely satisfactory, given the variability within GOLD groups, namely regarding hospitalizations and mortality.13

    • Optimal treatment sequence in COPD: Can a consensus be found?

      2016, Revista Portuguesa de Pneumologia (English Edition)
      Citation Excerpt :

      Table 2 and Fig. 1 summarize our proposals, suggestions and recommendations on COPD treatment sequence. Difficulties in early interventions (GOLD stage 1 and 2) are mainly due to low compliance, with increased mortality rate regardless of the type of therapy.12 A patient with dyspnea and fatigue will be more likely to comply with treatment whereas a less symptomatic patient will tend to be non-compliant.

    • New drug therapies for COPD

      2014, Clinics in Chest Medicine
    • The Diagnosis and Treatment of COPD and Its Comorbidities

      2023, Deutsches Arzteblatt International
    View all citing articles on Scopus
    View full text