Markers of exacerbation severity in chronic obstructive pulmonary disease

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event.

The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease

“…Thus, we cannot discount the possibility that longterm use of inhaled corticosteroids may reduce CRP levels in COPD. Second, we did not measure inflammatory biomarkers from lung samples due to a variety of technical and logistical constraints, including lack of standardization of sample collection, invasiveness of the procedure, and poor patient tolerability, that limit their application (47). Blood measurements, on the other hand, are more robust and are standardized.…”

Serum Amyloid A Is a Biomarker of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

“…A multivariable, ordinal logistic regression model that included FEV 1 % predicted was then developed to adjust for between-patient differences in the underlying disease severity and susceptibility to more severe AECOPD. To determine cutoff values for blood marker levels to potentially predict severe AECOPD, severity was subsequently defined as a binary categorical outcome (level I vs. level II/III) (30). AUC ROC analysis was used to measure the utility of CRP and SAA to predict AECOPD severity.…”

Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

“…Indeed, it has been documented that high doses of physostigmine, another acetylcholinesterase inhibitor causes death through centrally mediated respiratory arrest (Anzueto et al , 1990; Futagawa et al , 2000; Duncan et al , 2001). Blunted chemoreflexes have been correlated to respiratory failure and death in other diseases, including COPD and CCHS, and in animal model of SIDS (Schaefer, 1949; Fahey and Hyde, 1983; Shea et al , 1993; Milerad et al , 1995; Gozal et al , 1996; St-John and Leiter, 1999; Hafstrom et al , 2002; Murai et al , 2003; Franciosi et al , 2006; Ucgun et al , 2006). …”

“…Second, children with congenital central hypoventilation syndrome (CCHS), characterized by severely blunted or even absent V E responsiveness to hypercapnia, require artificial ventilation (Shea et al , 1993; Gozal et al , 1996). Similarly, severe chronic obstructive pulmonary disease (COPD) patients who exhibit blunted V E response to hypercapnia and hypoxia are likely to develop respiratory failure (Schaefer, 1949; Fahey and Hyde, 1983; Franciosi et al , 2006; Ucgun et al , 2006). Third, blunted V E response to hypoxia may lead to V E dysfunction, as was shown in an animal model of sudden infant death syndrome (SIDS) (Milerad et al , 1995; St-John and Leiter, 1999; Hafstrom et al , 2002; Murai et al , 2003).…”