We searched Medline without date or language restrictions. Initial search phrases were “exacerbation[All Fields] and (“microbiota” [mesh terms] or “microbiota” [all fields] or “microbiome” [all fields])” and “disease [all fields] and exacerbation [all fields] and (“microbiology” [subheading] or “microbiology” [all fields] or “bacteria” [all fields] or “bacteria” [mesh terms])” where disease represents “cystic fibrosis”, “COPD”, “bronchiectasis”, “asthma”, or “pulmonary fibrosis”.
SeriesThe role of the microbiome in exacerbations of chronic lung diseases
Introduction
The natural histories of several chronic lung diseases include exacerbations, which are characterised by abrupt worsening of respiratory symptoms and pulmonary function. Exacerbations cause much of the morbidity, mortality, and expense of chronic lung diseases,1, 2, 3 and are associated with accelerated disease progression.4, 5, 6, 7 Exacerbations are also associated with viral exposure and bacterial growth in cultures of respiratory specimens, but the precise relation between resident bacteria, acute infection, and the pathogenesis of exacerbations is controversial.8, 9
In the past decade, new culture-independent techniques for microbial identification such as pyrosequencing have shown a previously unappreciated complexity to the bacterial microbiome in the respiratory tract.10 The lungs and airways, whether in health or in chronic or acute lung disease, harbour diverse communities of microbes that are undetected by conventional culture-based approaches. A new understanding of lung microbiology has called into question long-held beliefs with respect to the pathogenesis of exacerbations of chronic lung disease derived from a half-century of experimentation and observation using culture-based techniques.
Section snippets
What is an exacerbation?
Exacerbations of chronic lung disease are periods of acute worsening of respiratory symptoms. They arise abruptly, within hours to days, and generally prompt an escalation in therapy. Symptoms might include focal respiratory symptoms, such as cough, increased sputum production, dyspnoea, or wheeze, but might also include systemic features such as fever, fatigue, or malaise. The onset of symptoms often precedes worsening of lung function,11 although in some patients with impaired perception of
Modern techniques to study the lung microbiome
Although a comprehensive discussion of modern techniques would exceed the scope of this review, familiarity with basic principles is key to understanding the revelations and difficulties in the field.10, 14, 15
Lung microbiome studies have used various molecular techniques to characterise microbial communities in the respiratory tract, but the most commonly used modern method is high-throughput sequencing of the 16S rRNA gene, a small and highly conserved locus in bacterial DNA. A single
The microbial ecology and topology of the human respiratory tract
A key principle in the speciality of microbial ecology is that local environmental conditions determine the composition of microbial communities. An oft-cited tenet in the field is that “Everything is everywhere, but the environment selects.”32 The growth of a species, and its relative abundance in the microbial community, is a function of nutrient availability, temperature, pH, oxygen concentration, and various other environmental factors. Thus any investigation into the respiratory microbiome
COPD
Exacerbations of COPD are associated with high mortality, rapid decrease in lung function, and increased health-care costs.68 Frequency of exacerbations increases with severity of airway obstruction, but many patients experience exacerbations more frequently than would be predicted by disease severity alone (the so-called frequent exacerbator phenotype).69 Exacerbations are also associated with systemic inflammation,70 airway inflammation,60 and increased airway obstruction due to oedema,
Key lessons and directions for study
Despite the presence of airway inflammation in respiratory exacerbations, a consistent finding across disease states is the lack of evidence that exacerbations are attributable to acute bacterial infections of the airways. Of the eight culture-independent studies across COPD, cystic fibrosis and non-cystic fibrosis bronchiectasis that have compared patients’ respiratory specimens obtained at baseline and during exacerbations, all showed no change in the bacterial density or community diversity
Search strategy and selection criteria
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