Upper Airways Microbiota in Antibiotic-Naïve Wheezing and Healthy Infants from the Tropics of Rural Ecuador

Cárdenas, Paúl; Cooper, Philip J.; Cox, Michael J.; Chico, Martha; Arias, Carlos F.; Moffatt, Miriam F.; Cookson, William

doi:10.1371/journal.pone.0046803

Cited by 92 publications

(84 citation statements)

References 46 publications

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“…We do know that there are differences in the airway microbiome between severe asthmatic patients and controls, 52 but again, whether primary or secondary cannot be determined; however, data from Ecuador shows that treatment-naïve wheezers have a different microbiome from non-wheezy controls. 98 These findings do however underscore that just because a cell is present it does not mean it is the cause of harm, and also drives home the lesson that adult and paediatric STRA may have important dissimilarities.…”

Section: The Role Of the Neutrophilmentioning

confidence: 96%

Severe asthma in children

2017

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Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed. First, the diagnosis of asthma should be confirmed, then co-morbidities assessed. Next, a nurse-led assessment further characterizes the problem, conventionally categorizing the child as either having difficult asthma or severe therapy-resistant asthma. Here, we reassess in particular the interactions between, and management of, these two categories, highlighting that this dichotomous classification may need reconsideration. We use bronchoscopy and an intramuscular steroid injection to determine if the child has steroid-resistant asthma, using a novel, multidomain approach because the adult definition does not apply to around half the children we see. Finally, we highlight some mechanistic data which have emerged from this protocol such as the absence of T-helper 2 (TH2) cytokines even in eosinophilic severe asthma and the potential role of the innate epithelial cytokine IL-33, novel data on lineage negative innate lymphoid cells, which we can measure in induced sputum, and demonstrating that intraepithelial neutrophils are associated with better, not worse asthma outcomes. Severe paediatric asthma is very different from severe asthma in adults, and approaches must not be uncritically extrapolated from adult disease to children.

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Section: The Role Of the Neutrophilmentioning

confidence: 96%

Severe asthma in children

2017

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“…Genomic DNA was extracted from induced sputum according to a modified protocol provided with the QIAamp DNA mini kit (Qiagen, Manchester, UK) (18). Full details are provided in the online supplement.…”

Section: Dna Extractionsmentioning

confidence: 99%

“…Quadruplicate 25-ml PCRs were set up, amplified, purified, and prepared for sequencing as previously described (18). Full details are provided in the online supplement.…”

Section: Pyrosequencing and Sequence Analysismentioning

confidence: 99%

Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease

Molyneaux

Mallia

Cox

et al. 2013

Am J Respir Crit Care Med

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337

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Rationale: Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways. Objectives: To investigate the effect of rhinovirus infection on the airway bacterial microbiome. Methods: Subjects with COPD (n ¼ 14) and healthy control subjects with normal lung function (n ¼ 17) were infected with rhinovirus. Induced sputum was collected at baseline before rhinovirus inoculation and again on Days 5, 15, and 42 after rhinovirus infection and DNA was extracted. The V3-V5 region of the bacterial 16S ribosomal RNA gene was amplified and pyrosequenced, resulting in 370,849 high-quality reads from 112 of the possible 124 time points. Measurements and Main Results: At 15 days after rhinovirus infection, there was a sixfold increase in 16S copy number (P ¼ 0.007) and a 16% rise in numbers of proteobacterial sequences, most notably in potentially pathogenic Haemophilus influenzae (P ¼ 2.7 3 10 -20 ), from a preexisting community. These changes occurred only in the sputum microbiome of subjects with COPD and were still evident 42 days after infection. This was in contrast to the temporal stability demonstrated in the microbiome of healthy smokers and nonsmokers. Conclusions: After rhinovirus infection, there is a rise in bacterial burden and a significant outgrowth of Haemophilus influenzae from the existing microbiota of subjects with COPD. This is not observed in healthy individuals. Our findings suggest that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections.Keywords: rhinovirus; chronic obstructive pulmonary disease; bacteria; microbiome Chronic obstructive pulmonary disease (COPD) is a growing global health epidemic, predicted to be the fourth leading cause of mortality worldwide by 2030 (1). Despite the chronic nature of COPD, acute exacerbations are the major cause of mortality, accounting for almost 70% of health care costs and accelerating the progressive decline in lung function (2). The great majority of exacerbations are caused by respiratory infections with bacteria and viruses, each of which has been detected in about 50% of cases, with coinfection common (3). The concurrent presence of bacteria and viruses during exacerbations of COPD has been shown to be associated with a greater decline in lung function and prolonged hospital stay (3, 4).Current understanding of the interactions between viruses and bacteria in exacerbations of obstructive airway disease is based predominantly upon classical microbial culture techniques. These have suggested that the lower airways are sterile , has therefore supplied the information regarding J.F.'s contribution to the manuscript and his competing interests, and it is correct to the best of her knowledge.The funders had no role in stu...

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“…Bacteria may be present in amniotic fluid (23) whilst the bacteria in the newborn gut have been shown to be influenced by delivery mode with the microbiota sourced from the mother's vagina during delivery or from skin with caesarean section (24). Accumulation of further organisms continues during infancy and childhood as demonstrated by longitudinal studies of the gut (8) and cross-sectional studies of the respiratory tract (25).…”

Section: The Human Microbiotamentioning

confidence: 99%