Reviews and feature article
Clinical phenotypes of chronic obstructive pulmonary disease and asthma: Recent advances

https://doi.org/10.1016/j.jaci.2013.01.010Get rights and content

Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases, both of which are characterized by airflow limitation. Although both represent distinct pathogenic entities, there can be significant clinical and physiologic overlap between the 2 disorders, creating potential management difficulties for clinicians. Although practice guidelines for both conditions outline diagnostic and management strategies, asthma and COPD are highly heterogeneous, and the symptoms of many patients remain poorly controlled despite adherence to current guidelines. Recent advances in phenotyping studies have elucidated heterogeneity in these airway diseases and might represent the best opportunity to enhance diagnosis, predict outcomes, and personalize treatments in patients with asthma and those with COPD. This review will focus on recent advances in describing phenotypic heterogeneity in asthma and COPD, including the evaluation of multiple clinical variables, molecular biomarkers, physiologic and radiologic data, and factors associated with disease progression and frequent exacerbations.

Section snippets

Guideline-based approaches to differentiating asthma and COPD

Guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) state that a clinical diagnosis of COPD should be considered in adult patients with dyspnea, chronic cough, sputum production, and a history of significant tobacco exposure. Typically, patients will present with cough, sputum production, or shortness of breath, and once such patients are identified, the diagnosis of COPD further necessitates the presence of a postbronchodilator FEV1/forced vital capacity (FVC)

Clinical phenotyping in patients with COPD and prediction of mortality

One approach to phenotyping in patients with COPD involves the use of clinical, physiologic, and radiologic data to elucidate factors that dictate disease heterogeneity and therefore might be relevant to diagnosis, prognosis, or both. The application of analytic approaches, such as cluster analysis, has advanced the study of phenotypes, facilitating the identification of unique groups of related variables in an attempt to identify factors that might relate to both underlying disease biology and

Exacerbation phenotyping in patients with COPD

As the disease progresses, the natural history of COPD is marked by exacerbations, which cause worsening of airflow limitation and increased symptoms in the context of infection, an increase in underlying airway inflammation, or both. COPD exacerbations negatively affect quality of life and accelerate the overall decrease in lung function, increasing both morbidity and mortality.13, 14, 15 Given the importance of these events in the natural history of COPD, it is important to recognize and

Radiologic phenotyping of patients with COPD

Ongoing large cohort studies in which imaging data are being obtained provide the opportunity to link radiologic phenotypes with disease status and outcomes in patients with COPD. One such study that has recently facilitated significant advances in this regard is the COPDGene study, a multicenter observational study designed to identify genetic factors associated with COPD. Participants in this study undergo inspiratory, whole-lung, volumetric multidetector computed tomographic (CT) scanning19

Phenotypes related to physiologic progression of COPD

Historically, the rate of decrease in FEV1 has been the most widely used means to monitor disease progression in patients with COPD. Although the classic Fletcher-Peto curve defined susceptibility phenotypes of patients with COPD based on rate of lung function decrease over time,26 the variables that predict which patients will progress rapidly and which will not are still not well understood. To address the issue of intersubject variability in the rate of lung function decrease, Nishimura etĀ al

Inflammatory phenotypes in asthmatic patients

Asthma has long been recognized as a heterogeneous condition, and as reviewed elsewhere,31 substantial progress has been made in describing biologically meaningful phenotypes, many of which have implications for clinical management. One of the earliest approaches to phenotyping asthma in a clinically relevant manner was to use the inflammatory cell composition of induced sputum. To do this, Green etĀ al32 performed a randomized trial comparing guideline-based therapy with therapy targeted to

Cluster analyses to identify asthma phenotypes

Although focusing on molecular signatures in phenotyping asthma is attractive, it requires biologic samples, which are not always readily available in clinical practice. As described in patients with COPD, investigators have focused on phenotyping asthma by clustering patients using several more easily determined clinical variables. Haldar etĀ al38 used K-means cluster analysis to identify phenotypically similar groups in 3 independent asthma populations. The variables selected included age of

Phenotypes related to asthma progression

Some patients with asthma experience a progressive decrease in lung function similar to that observed in patients with COPD, possibly because of variations in disease persistence, patterns of inflammation, and airway remodeling. The rate of lung function decrease in asthmatic patients is variable, possibly because of differences in phenotype. Data from the Childhood Asthma Management Program (CAMP) have provided insight in this regard. Using data from the CAMP study to perform a secondary

Exacerbation phenotyping in asthmatic patients

Exacerbations in asthmatic patients, as is the case in those with COPD, are associated with loss of lung function. Bai etĀ al42 followed 93 adults with moderate-to-severe asthma over 11 years to assess the effects of exacerbations on lung function. There were 186 exacerbations in 60% of the subjects enrolled in this study over the 11 years, and subjects with frequent exacerbations had lower lung function, with an accelerated decrease in FEV1 (32 vs 15 mL). Although the authors were not able to

Phenotypic overlap between asthma and COPD

Some patients with COPD demonstrate features that overlap with asthma.44 Diagnostic criteria for this ā€œphenotypic overlapā€ have been proposed, including positive bronchodilator response, eosinophilia in sputum, personal history of asthma before age 40 years, high total IgE level, and a personal history of atopy.45 It is important to recognize that this group of patients has been systematically excluded from many clinical trials, and therefore evidence about their management is limited despite

Phenotyping and future implications for therapy

Whereas the treatment of asthma has the use of anti-inflammatory therapies (particularly ICSs) as its cornerstone, with prolonged bronchodilation brought to bear in more advanced disease stages, in the treatment of COPD, prolonged bronchodilation is at the forefront of management. Although treatment of these 2 disorders is comprehensively reviewed in guideline documents,1, 2 the data reviewed above could be construed to suggest that the identification of clinical, cellular, and molecular

References (46)

  • A. Agusti et al.

    Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine

    Am J Respir Crit Care Med

    (2011)
  • D.G. Parr

    Patient phenotyping and early disease detection in chronic obstructive pulmonary disease

    Proc Am Thorac Soc

    (2011)
  • A.C. Dornhorst

    Respiratory insufficiency

    Lancet

    (1955)
  • B.S. Everitt et al.

    Cluster Analysis

    (2011)
  • P.R. Burgel et al.

    Clinical COPD phenotypes: a novel approach using principal component and cluster analyses

    Eur Respir J

    (2010)
  • P.R. Burgel et al.

    Clinical COPD phenotypes identified by cluster analysis: validation with mortality

    Eur Respir J

    (2012)
  • B.R. Celli et al.

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

    N Engl J Med

    (2004)
  • F.J. Martinez et al.

    Longitudinal change in the BODE index predicts mortality in severe emphysema

    Am J Respir Crit Care Med

    (2008)
  • C.G. Cote et al.

    Pulmonary rehabilitation and the BODE index in COPD

    Eur Respir J

    (2005)
  • G.C. Donaldson et al.

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

    Thorax

    (2002)
  • R.E. Kanner et al.

    Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study

    Am J Respir Crit Care Med

    (2001)
  • T.A. Seemungal et al.

    Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2000)
  • J.R. Hurst et al.

    Susceptibility to exacerbation in chronic obstructive pulmonary disease

    N Engl J Med

    (2010)
  • Cited by (0)

    Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD

    View full text