Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis

Abstract

Pneumonia is a major cause of morbidity and mortality for which no new methods of treatment have entered clinical practice since the discovery of antibiotics. Innovations in the techniques of culture-independent microbial identification have shown that the lungs, previously deemed sterile in the absence of infection, contain diverse and dynamic communities of microbes. In this Personal View, we argue that these observations have shown the inadequacy of traditional conceptual models of lung microbiology and the pathogenesis of pneumonia, hampering progress in research and practice. We propose three new conceptual models to replace the traditional models of lung microbiology: an adapted island model of lung biogeography, the effect of environmental gradients on lung microbiota, and pneumonia as an emergent phenomenon propelled by unexplored positive feedback loops. We argue that the ecosystem of lung microbiota has all of the features of a complex adaptive system: diverse entities interacting with each other within a common space, showing interdependent actions and possessing the capacity to adapt to changes in conditions. Complex adaptive systems are fundamentally different in behaviour from the simple, linear systems typified by the traditional model of pneumonia pathogenesis, and need distinct analytical approaches.

Figure 1. An adapted island model of lung biogeography

Immigration and extinction rates for an island as a function of number of species present (A). Effect of island size and proximity to large land mass on the intersection of immigration and extinction curves (B). Application of model to microbiota within the respiratory tract (C). Speculated positive immigration and negative extinction factors for lung microbiota (D). S=equilibrium of species richness. Figure 1A and 1B reproduced with permission from MacArthur and Wilson.

Figure 2. Environmental gradients in the lungs

Regional differences in gas exchange in the upright lungs (A). Reproduced with permission from West. Mean wall and air temperature in the tracheobronchial tree of human beings after hyperventilating cold air (B). Reproduced with permission from Ingenito. Relative abundance of two diatoms (Cyclotella and Asterionella) in 78 samples of water from Lake Michigan, USA, plotted against ratio of ambient silicate to phosphate (C). Reproduced with permission from Tilman. A.f. dominant=Asterionella formosa dominant. C.m. dominant=Cyclotella meneghiniana dominant.

Figure 3. Example of a potential positive feedback explaining the abrupt emergence of pneumonia from pre-existing homoeostasis

Dotted lines indicate inhibition, resulting in negative feedback loops. Solid lines indicate promotion, resulting in a positive feedback loop. This is merely one of many possible feedback loops mediating the pathogenesis of pneumonia