The airway microbiota in early cystic fibrosis lung disease

Abstract

Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie.

Glycoprotein A as a biomarker of pulmonary infection and inflammation in children with cystic fibrosis

“…There are many possible reasons for this. Our knowledge of the pulmonary microbiome in CF in young children continues to evolve and ultimately, the number of different proinflammatory organisms isolated from BAL at a single point in time is unlikely to be a uniform marker of severity of the infection. It is possible that GlycA levels do not have sufficient sensitivity to reflect subtle changes in early infection‐associated inflammation.…”

Mucoviscidosis: fisiopatología, genética, aspectos clínicos y terapéuticos

“…Los nuevos métodos de identificación molecular revelan una extrema diversidad bacteriana, incluyendo gérmenes anaerobios de origen ambiental y de la cavidad bucal. Estas comunidades bacterianas limitan de manera progresiva su diversidad a medida que evolucionan [21] .…”

“…La historia natural de la colonización comienza con la implantación de cepas en las vías respiratorias superiores, seguida de una colonización traqueobronquial intermitente [21] . A pesar de una respuesta inmunitaria suficiente para prevenir la invasión sistémica, P. aeruginosa no puede ser erradicada del huésped y desarrolla una infección crónica.…”

Rebuttal from Stephen M. Stick and André Schultz

“…2018), although the associations of microbiota with inflammation and lung damage are complex (Frayman et al . 2017). Nonetheless it seems highly unlikely that pathogen colonisation that is undetectable by BAL and conventional culture techniques can be responsible for the extent of early lung disease that is identified by computed tomography and BAL (Sly et al .…”

“…Few of these infants had evidence of infection with pathogens in bronchoalveolar lavage (BAL) fluid using standard microbiological techniques. Recent studies using sensitive RNA sequencing techniques suggest a transition from an essentially sterile airway microenvironment to one that is dominated by recognised CF lung pathogens at a time when airway inflammation is already established (Muhlebach et al 2018), although the associations of microbiota with inflammation and lung damage are complex (Frayman et al 2017). Nonetheless it seems highly unlikely that pathogen colonisation that is undetectable by BAL and conventional culture techniques can be responsible for the extent of early lung disease that is identified by computed tomography and BAL (Sly et al 2009).…”