Pneumocystis: a novel pathogen in chronic obstructive pulmonary disease?

Abstract

Chronic obstructive pulmonary disease (COPD) results in significant morbidity and mortality. Smoking has long been recognized as the primary risk factor for development of COPD, but factors determining the severity or pattern of disease in smokers are largely unknown. Recent interest has focused on the potential role of infectious agents and the associated host response in accelerating progression of airway obstruction or in perpetuating its progression following discontinuation of tobacco exposure. Pneumocystis jirovecii is a fungal pathogen that causes pneumonia in immunocompromised individuals. Recent evidence has linked this organism with COPD. Using sensitive molecular techniques, low levels of Pneumocystis have been detected in the respiratory tract of certain individuals and termed colonization. Several findings support the theory that colonization with Pneumocystis is involved in the "vicious circle" hypothesis of COPD in which colonization with organisms perpetuates an inflammatory and lung remodeling response. Pneumocystis colonization is more prevalent in smokers and in those with severe COPD. The presence of Pneumocystis in the lungs, even at low levels, produces inflammatory changes similar to those seen in COPD, with increases in numbers of neutrophils and CD8(+) lymphocytes. HIV-infected subjects who have had PCP develop permanent airway obstruction, and HIV-infected patients have a high prevalence of both emphysema and Pneumocystis colonization. In addition, a non-human primate model of colonization shows development of airway obstruction and radiographic emphysema. Additional studies are needed to confirm the role of Pneumocystis in the pathogenesis of COPD, given that this agent might be a treatable co-factor in disease progression.

Figure 1

Comparison of FEV₁ and FEV₁/FVC in Pneumocystis-colonized subjects and Pneumocystis negative. p = 0.006 for both comparisons. Abbreviations: FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second, percent predicted.

Figure 2

Association of GOLD stage and prevalence of Pneumocystis colonization. Reproduced with permission from American Journal of Respiratory and Critical Care Medicine. Abbreviations: GOLD, Global Health Initiative on Obstructive Lung Disease.

Figure 3

Change in forced expiratory volumes and forced expiratory flow values for non-colonized monkeys from baseline (uninfected) to follow-up (SHIV-infected, Pneumocystis-negative) and for Pneumocystis-colonized monkeys from baseline (uninfected) to follow-up (SHIV-infected, Pneumocystis-colonized). Average follow-up of 8 months. * p = 0.02 for comparison of change in FEV_0.4 and FEF₂₅–₇₅ in non-colonized versus Pneumocystis-colonized. Abbreviations: FEV_0.4, forced expiratory volume during first 0.4 seconds; FEF₂₅–₇₅, forced expiratory flow over mid 50% of forced vital capacity; Pc, Pneumocystis.