Pathogen-directed therapy in acute exacerbations of chronic obstructive pulmonary disease

Abstract

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.

Figure 1.

Upper (URT) and lower respiratory tract (LRT) symptoms of patients with chronic obstructive pulmonary disease in vivo experimentally infected with rhinovirus. A 3- to 4-day gap between the peak of cold symptoms and the peak of lower respiratory symptoms was documented. Reproduced by permission from Reference .

Figure 2.

(A) Effect of antibiotics versus placebo on short-term mortality. (B) Effect of antibiotics versus placebo on treatment failure, defined as no resolution or deterioration of symptoms after trial medication of any duration or death. CI, confidence interval. Reprinted by permission from Reference .

Figure 2.

(A) Effect of antibiotics versus placebo on short-term mortality. (B) Effect of antibiotics versus placebo on treatment failure, defined as no resolution or deterioration of symptoms after trial medication of any duration or death. CI, confidence interval. Reprinted by permission from Reference .

Figure 3.

Forest plot showing nine studies grouped according to severity of exacerbation. The upper five studies included patients with mild to moderate exacerbations and the four studies below included patients with severe exacerbations. The x axis represents the odds ratio for treatment failure. Reprinted by permission from Reference .

Figure 4.

Proportion for each of four viral pathogens isolated during each calendar month over a 6-month period of study in Tecumseh, Michigan. Reprinted by permission from Reference .