Key Point

The heterogeneity of COPD may be reducible to just four factors. Severity of COPD, measured by spirometry, appears to occur independently of inflammation assessed in sputum.

LEIDEN, NETHERLANDS—COPD is considered to be a heterogeneous disease, with many influences on its clinical, physiologic, and pathologic presentation and course. Recent research supports this hypothesis by categorizing multiple features of COPD into four separate and independent factors, using factor analysis:

Factor 1: Airflow limitation (postbronchodilator FEV₁, the ratio of FEV_1, to inspiratory vital capacity [FEV₁/IVC], and the ratio of residual volume to total lung capacity [RV/TLC]).

Factor 2: Asthma-like components such as reversibility of airflow limitation, serum immunoglobulin E (IgE) levels, and the concentration of methacholine needed to produce a 20% drop in FEV₁.

Factor 3: Exhaled nitric oxide (eNO) levels.

Factor 4: Sputum percentages of neutrophils and eosinophils.

These results suggest that airflow limitation may be separate from eosinophilic and neutrophilic inflammation.¹

Thérèse S. Lapperre, MD, and colleagues conducted a factor analysis of 114 COPD patients with moderate to severe disease (postbronchodilator FEV₁ range, 40.8% to 77.7% of predicted). None of the study participants had used inhaled steroids for at least six months. Most (63.2%) were current smokers. “These different components represent different and complementary information about COPD patients and their pathophysiology,” said Dr. Lapperre, who is with the Leiden University Medical Center in the Netherlands. “It needs to be examined whether the clinical evaluation of patients with COPD should include each of these complementary entities,” she added.

WHAT COPD BOILS DOWN TO

Dr. Lapperre and colleagues found that the above four factors accounted for 63.6% of the total variance in COPD. In a univariate model, reversibility to albuterol was not associated with inflammatory parameters such as sputum neutrophil and eosinophil levels and eNO. RV/TLC was associated with sputum percentage of neutrophils and postbronchodilator FEV₁, whereas airway hyperresponsiveness and FEV₁/IVC were associated with eNO levels. FEV₁/IVC was related to sputum percentage of eosinophils.

Airflow limitation and lung hyperinflation were combined in the first factor. Reversibility of FEV₁, airway hyperresponsiveness, and total serum IgE composed the second factor, indicating that these measurements represent separate dimensions in the assessment of COPD. That neutrophil and eosinophil levels and eNO composed factors 4 and 3, respectively, suggests that both of these disease aspects are at least partially independent from the traditionally used functional disease markers of COPD.

LUNG FUNCTION AND INFLAMMATION DISTINCT FACTORS IN COPD

It is noteworthy that none of the lung function parameters overlapped with the inflammatory factors, indicating that these two dimensions are separate from one another in COPD. The authors hypothesize that airway and lung tissue restructuring may cause airflow limitation, but this process occurs independently of neutrophilic and eosinophilic inflammation. In other words, airflow limitation could be induced by other factors.

Factor analysis has been used in the past to evaluate the pathophysiology of COPD, but these studies did not include inflammatory markers. It remains to be seen whether the clinical evaluation of patients with COPD should include each of the four factors that were identified in the present study. Dr. Lapperre suggested that including pathology such as T-lymphocyte, B-cell, and CD8+ cell counts in the airway wall in the factor analysis might shed some light on their relation with other inflammatory parameters suggested to be involved in the course of the illness. Additionally, said Dr. Lapperre, “a longitudinal study providing the natural history of airway inflammation in COPD will be very informative to investigate associations with progression of COPD and influences of anti-inflammatory treatments,” she concluded.

—Tamara Gibb

Reference
1. Lapperre TS, Snoeck-Stroband JB, Gosman MME, et al. Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170:499-504.

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