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

https://doi.org/10.1016/S2213-2600(14)70028-1Get rights and content

Summary

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.

Introduction

A century ago, two decades after Pasteur's initial description of the pneumococcus,1 Sir William Osler described pneumonia as “captain of the men of death”, the “most widespread and fatal of all acute diseases”, “a self-limited disease, which can neither be aborted nor cut short by any known means at our command”.2 The subsequent discovery and development of antibiotics and vaccines improved the treatment and prevention of pneumonia, and its prominence as a major public health concern decreased in the second half of the 20th century.3 However, antibiotic development has stagnated, drug-resistant organisms are increasingly common,4 and no novel treatment methods for management of pneumonia have been incorporated into practice since the beginning of antibiotic therapy 75 years ago. Respiratory infections remain a huge source of mortality and morbidity, responsible for a greater global burden of disease than are cancer, ischaemic heart disease, or diabetes.5

Key messages

  • Novel techniques of culture-independent microbial identification have shown that the lungs, even in the absence of infection, contain diverse and dynamic communities of microbes

  • These observations have shown the inadequacy of traditional models of lung microbiology and the pathogenesis of pneumonia

  • Borrowing pivotal concepts from the fields of ecology and complexity theory, we propose three novel conceptual models of lung microbiology and pneumonia pathogenesis

  • The respiratory tract is a single ecosystem extending from the nares to the alveoli, comprising a continuous, and continuously varying, microbial topography

  • The number of microbial species at a given site in the respiratory tree is an integrated function of many immigration and extinction factors

  • The lungs and airways are spatially heterogeneous in temperature, oxygen tension, pH, nutrient density, and local anatomy and host defence, all of which affect local microbiological growth conditions

  • The development of pneumonia is an abrupt and emergent phenomenon of disruption in the complex homoeostasis of the lung microbial ecosystem that results from undescribed positive feedback loops arising within a complex adaptive system

In the past decade, novel culture-independent techniques have shown that the lower respiratory tract, previously deemed sterile, contains diverse communities of microbes, even without clinical evidence of infection.6 Novel insights have shown a previously unappreciated complexity to lung microbiology and the pathogenesis of respiratory infections. We argue that the conventional model of the pathogenesis of pneumonia—the rapid growth of an invasive organism in a previously sterile area of the body—has proven inadequate for the appropriate contextualisation of observations from modern lung microbiome studies, and has probably hampered progress in treatment and prevention of pneumonia. The use of inappropriate conceptual frameworks results in imprecise terms, poorly framed debates, and confines the imaginations and approaches of researchers and clinicians.

In this Personal View, we propose three new concepts to replace the traditional models of lung microbiology that shape our understanding of pneumonia and its emergence from a previously healthy lung environment. These concepts include an adapted island model of lung biogeography, the effect of environmental gradients on lung microbiota, and pneumonia as an emergent phenomenon propelled by largely unexplored positive feedback loops. For each proposed conceptual model, we summarise the conventional method it is designed to replace, discuss our proposed model, review relevant published work, and provide areas of further study and potential implications for clinical care.

Section snippets

Conceptual model 1: an adapted island model of lung biogeography

Modern textbooks of pathology7 and clinical medicine8 follow the long tradition of dividing the anatomy of the respiratory tract and its associated infections into those of upper and lower compartments, typically defined as the airways and parenchyma above and below the larynx or trachea. The term pneumonia is often used interchangeably with lower respiratory tract infection.

The upper airways have long been known to be replete with diverse and abundant communities of microbes, but even recent

Conceptual model 2: the effect of environmental gradients on lung microbiota

As discussed in conceptual model 1, the respiratory tract has traditionally been divided into upper and lower compartments. In characterisation of the microbiology of lower respiratory tract infections, modern textbooks and reviews list pulmonary pathogens collectively without specifying each microbe's predilection for specific regions of lung anatomy.7, 8, 41 With few conspicuous exceptions (aspiration pneumonia favouring dependent zones and reactivation tuberculosis favouring the apices),

Conceptual model 3: the lung microbial ecosystem is a complex adaptive system within which pneumonia is an emergent and disruptive phenomenon

The conventionally understood mechanism of pathogenesis of bacterial pneumonia is a natural extension of the tenet that the lungs are sterile: a suitably large inoculum of a pathogenic species enters the lower respiratory tract and overwhelms host defences, resulting in rapid and unrestrained growth of a bacterial species. Within this model, few factors should be all that is needed to predict the features of a given pneumonia: size of inoculum, virulence of the bacterial species, and strength

Conclusion

The traditional conceptual models of lung microbiology are inadequate, as shown by observations using culture-independent techniques of bacterial identification. Using pivotal concepts from the fields of ecology and complexity theory, we have proposed three new conceptual models for the study of lung microbiology (table 2). These models provide a theoretical framework for novel approaches to understanding of the pathogenesis, prevention, and treatment of respiratory infections.

Search strategy and selection criteria

We searched PubMed and Web of Science using the terms “((lung) OR (pulmonary)) AND ((microbiome) OR (16S) OR (pyrosequencing) OR (culture-independent))” with no date or language restrictions to identify relevant studies of the lung microbiome. We then manually screened titles and abstracts to exclude unrelated studies. We read all studies in human beings describing or reviewing bacterial communities in the lung in individuals with and without disease. In developing the conceptual models, we

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