Respiratory Impairment and Systemic Inflammation in Cedar Asthmatics Removed from Exposure

Background

Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation.

Methods

Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC₂₀ (methacholine concentration that produces 20% fall in FEV₁ (forced expiratory volume at 1 second)) sputum cellularity and select T_h1/T_h2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines.

Results

40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC₂₀ had increased by 2.0 mg/ml; the FEV₁ decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV₁ component (correlation with interferon-gamma = −0.46, p = 0.005).

Conclusion

Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation.     

Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

Background

Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR).

Methods

Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro.

Results

Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro.

Conclusion

Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.     

过敏性哮喘动物模型在致敏、哮喘发作和气道高反应性等方面的应用研究

过敏性哮喘的发病率呈上升趋势。使用了几十年的主要治疗药物肾上腺糖皮质激素副作用较大,因此发现好的预防和治疗方法成为迫切要解决的问题。动物模型是研究人类疾病的重要手段,但不少疑难病的发病机理不明确,因而制备的动物模型和人类疾病的相似度有差异。但I型变态反应作为过敏性哮喘的发病机理是比较明确的,据此制备的动物模型和人类的哮喘就有很高的相近度,结果的可信度就较高。本文回顾了哮喘动物模型制备的基本方法和某些重要的细节。着重讨论了当今最常用的气道高反应性模型的优劣。如果综合运用不同特点的模型尤其是能观察记录哮喘发作全过程包括速发和迟发反应的模型,将可以更直接地探索哮喘发病过程和治疗药物。对气道重塑及基因敲除和转基因技术在动物模型中的研究和使用也做了一般性论述。动物模型将是一个有力的工具为最后有效地预防和治疗过敏性哮喘找到突破口。     

Deficiency of RAMP1 Attenuates Antigen-Induced Airway Hyperresponsiveness in Mice

Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP) is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR), and receptor activity-modifying protein 1 (RAMP1). RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR interface to assist in the treatment of asthma.     

Perceived Food Hypersensitivity Relates to Poor Asthma Control and Quality of Life in Young Non-Atopic Asthmatics

Background

The relationship between perceived food hypersensitivity in asthmatics, food allergen sensitization, asthma control and asthma-related quality of life has not been studied.

Objective

Our aim was to study the prevalence of perceived food hypersensitivity in a cohort of young asthmatics, its relation to food allergen sensitization, and any correlation to asthma control and asthma-related quality of life.

Methods

Perceived food hypersensitivity, as well as IgE sensitization to common food allergens, levels of exhaled nitric oxide (FeNO), and blood eosinophil counts (B-Eos) were assessed in 408 subjects (211 women) with asthma, aged (mean ± SEM) 20.4 ± 0.3 years. Subjects filled out the Asthma Control Test (ACT) and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Inflammation was assessed by means of FeNO and B-Eos.

Results

Fifty-three per cent of subjects reported food hypersensitivity. A corresponding food allergen sensitization was found in 68% of these subjects. Non-atopic subjects with perceived food hypersensitivity (n = 31) had lower ACT (19 (15 - 22) vs. 21 (20 - 23), p < 0.001) and Mini-AQLQ -scores (5.3 (4.3 - 6.1) vs. 6.1 (5.5 - 6.5), p < 0.001) than subjects with no food hypersensitivity (n = 190), despite lower levels of FeNO and B-Eos (p < 0.05).

Conclusions and Clinical Relevance

Food hypersensitivity was commonly reported among young asthmatics. In a majority of cases, a corresponding food allergen sensitization was found. A novel and clinically important finding was that non-atopic subjects with perceived food hypersensitivity were characterized by poorer asthma control and asthma-related quality of life.     

通光散汤对小鼠哮喘模型气道高反应性和气道炎症的影响

目的观察通光散对小鼠哮喘模型气道反应和气道炎症的影响。方法35只6周龄BALB／c小鼠随机分为哮喘模型组、正常对照组和药物实验组。模型组和药物组以鸡卵白蛋白（OVA）致敏、激发;药物组在最后一次致敏后每天灌胃给予通光散汤0．72mL（相当于0．04g生药）;对照组以等体积的Ns代替OVA致敏、激发。末次激发48h后处理小鼠：无创法测定小鼠的气道高反应性,观察气道阻力变化;支气管肺泡灌洗液（BALF）行细胞学分类;观察肺组织的病理变化。结果①药物组小鼠气道阻力的变化与模型组相比明显下降,差异显著（P＜0．05）;②药物组BALF白细胞总数和Eos（％）与模型组相比明显降低（P＜0．05）。③模型组小鼠肺脏组织支气管、血管黏膜下和周围肺组织有明显的炎症细胞浸润,大量炎症细胞向支气管和血管迁移,上皮细胞部分有脱落,部分可见黏液栓,血管壁明显水肿;治疗组小鼠肺组织炎性细胞浸润和管腔黏液分泌情况较模型组明显减轻,气道粘液的分泌量得到明显的控制。结论通光散汤对小鼠哮喘模型气道高反应性和气道炎症有显著抑制作用。     

Pulmonary Inflammation and Airway Hyperresponsiveness in a Mouse Model of Asthma Complicated by Acid Aspiration

Several studies have indicated a strong association between asthma and aspiration of stomach contents. However, the complex association between these inflammatory processes has not been studied extensively in animal models. In the present study, we developed an animal model to evaluate the inflammatory cell, chemokine, and airway responses to asthma complicated by aspiration. The model was produced by sensitizing mice to cockroach allergens from house-dust extracts. Mice with asthma-like airway responses then were inoculated intratracheally with either an acidic solution or saline. Acid aspiration increased airway hyperresponsiveness in mice with asthma for at least 8 h. After 6 h, the combined injury caused an additive, not synergistic, increase in airway hyperresponsiveness and neutrophil recruitment to the airways. Although cysteinyl leukotrienes in bronchoalveolar lavage fluid were higher after acid aspiration, treatment with a receptor antagonist before aspiration did not diminish airway hyperresponsiveness. Vagal mechanisms reportedly mediate airway responses in acid aspiration; however, pretreatment with an anticholinergic agent did not reduce airway responses to acid. These results are consistent with an effective model of the acute effects of aspiration on the allergic lung. Further studies could examine how various forms of aspiration influence the severity of asthma.Abbreviations: BAL, bronchoalveolar lavage; MIP, macrophage inflammatory protein; Penh, enhanced pauseAsthma is an escalating public health problem in children and adults.⁴⁹ In patients with asthma, exaggerated immune responses to allergens produce lung inflammation and dysfunction. These responses lead to the characteristic airway hyperresponsiveness, obstructed airflow, and clinical symptoms associated with asthma.⁴⁹ Although several conditions aggravate asthma, much recent attention has focused on the provocative association between asthma and aspiration of stomach acid. The prevalence of gastroesophageal reflux in some asthma patient populations is greater than 50% ²¹ and significantly exceeds the prevalence in nonasthmatic populations.^20,47 This finding suggests an association between the 2 diseases and the possibility that gastroesophageal reflux promotes or aggravates symptoms that lead to the diagnosis asthma. In fact, several studies have shown a decrease in asthma symptoms after medical or surgical treatment of gastroesophageal reflux.^4,11,18,19Stomach acid may exacerbate asthma symptoms through 2 mechanisms. The first is a vagal reflex initiated in response to acid in the esophagus. Clinical studies in humans^20,50 and experimental studies in animals^34,48 have shown that acid in the esophagus promotes neurologic responses leading to bronchoconstriction and impaired airway function. Esophageal acid also may cause substance P- mediated neurogenic inflammation.¹⁶ The second mechanism is due to aspiration into the airways, which also has been documented to occur in asthma patients.²⁵ The presence of acid in the trachea increases airway hyperresponsiveness in anesthetized animals through vagal mechanisms,⁴⁸ particularly in the presence of preexisting lung inflammation.³² In addition to neurologic responses, aspiration of acid induces a pattern of pulmonary inflammation characterized by the release of proinflammatory cytokines and neutrophil recruitment.^26,31 That inflammation may also increase airway responsiveness.⁶Well-established models for both asthma^6,10,14,27 and aspiration^31,39 studies are available currently. However, the patterns of inflammation that occur after sequential insults are complex and may not be predicted by studies of the responses to individual insults.⁸ In addition, the mechanisms for exacerbation of airway hyperresponsiveness by aspiration in asthma have been limited to use of anesthetized animals. A model that allows recovery from the anesthesia after delivery of the aspirate permits the development and evaluation of pulmonary changes under more physiologic conditions. Therefore, the goals of this study were to: (1) describe acute exacerbation of asthma by acid aspiration in mice after recovery from anesthesia; (2) determine the effects of combined insults on airway hyperresponsiveness; and (3) profile the cellular and cytokine responses to the combined insults to assess potential mechanisms for the pulmonary responses to asthma complicated by aspiration.     

Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 h exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 h of environmental exposure to Florida red tide aerosols for up to 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.     

过表达XB130抑制哮喘小鼠气道高反应性和气道炎症

目的:研究XB130在哮喘小鼠气道高反应(airway hyperresponsiveness,AHR)和气道炎症中的作用。方法:36只C57小鼠分为4组:正常对照组(Control,CON)、哮喘组(Asthma,AS)、腺病毒载体组(Ad-vector+AS)和腺病毒过表达XB130组(Ad-XB130+AS)。采用卵白蛋白(ovalbumin,OVA)建立小鼠过敏性哮喘模型,后两组小鼠分别尾静脉注射Ad-vector和Ad-XB130。最后一次雾化吸入后24小时进行气道高反应试验,收集支气管灌洗液(bronchi alveolar lavage fluids,BALF)。采用RT-PCR和Western blotting方法检测XB130表达。ELISA法检测血清中OVA特异性Ig E的含量。直接计数法计算BALF中嗜酸性粒细胞(eosinophile granulocyte,EOS)数量。ELISA方法用于检测BALF和肺组织中IL-4、IL-5、IL-13和IFN-γ的分泌。结果:哮喘小鼠肺组织中XB130表达减少,过表达XB130其m RNA和蛋白表达水平显著升高。过表达XB130降低醋甲胆碱(methacholine,Mch)诱导的气道高反应。与载体对照组(48±3)相比,XB130过表达(17±4)EOS数量显著减少。同时,过表达XB130(0.051±0.002)较载体对照组(0.128±0.007)Ig E含量减少。此外,XB130抑制哮喘小鼠中IL-4、IL-5和IL-13并促进IFN-γ分泌。结论:过表达XB130可抑制哮喘模型小鼠气道高反应性和炎症反应。     

Toll-Like Receptor Ligands LPS and Poly (I:C) Exacerbate Airway Hyperresponsiveness in a Model of Airway Allergy in Mice,Independently of Inflammation

It is well-established that bacterial and viral infections have an exacerbating effect on allergic asthma, particularly aggravating respiratory symptoms, such as airway hyperresponsiveness (AHR). The mechanism by which these infections alter AHR is unclear, but some studies suggest that Toll-like receptors (TLRs) play a role. In this study, we investigated the impact of TLR3 and TLR4 ligands on AHR and airway inflammation in a model of pre-established allergic inflammation. Female BALB/c mice were sensitised and challenged intranasally (i.n.) with either PBS or ovalbumin (OVA) and subsequently i.n. challenged with poly (I:C) (TLR3) or LPS (TLR4) for four consecutive days. The response to methacholine was measured in vivo; cellular and inflammatory mediators were measured in blood, lung tissue and broncheoalveolar lavage fluid (BALF). OVA challenge resulted in an increase in AHR to methacholine, as well as increased airway eosinophilia and TH2 cytokine production. Subsequent challenge with TLR agonists resulted in a significant increase in AHR, but decreased TLR-specific cellular inflammation and production of immune mediators. Particularly evident was a decline in LPS-induced neutrophilia and neutrophil-associated cytokines following LPS and poly (I:C) treatment. The present data indicates that TLRs may play a pivotal role in AHR in response to microbial infection in allergic lung inflammation. These data also demonstrate that aggravated AHR occurs in the absence of an exacerbation in airway inflammation and that allergic inflammation impedes a subsequent inflammatory response to TLRs. These results may parallel clinical signs of microbial asthma exacerbation, including an extended duration of illness and increased respiratory symptoms.     

Key Role of Group V Secreted Phospholipase A2 in Th2 Cytokine and Dendritic Cell-Driven Airway Hyperresponsiveness and Remodeling

Background

Previous work has shown that disruption of the gene for group X secreted phospholipase A₂ (sPLA₂-X) markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA₂s in the mammalian genome, the involvement of other sPLA₂s in the asthma model is possible – in particular, the group V sPLA₂ (sPLA₂-V) that like sPLA₂-X is highly active at hydrolyzing membranes of mammalian cells.

Methodology and Principal Findings

The allergen-driven asthma phenotype was significantly reduced in sPLA₂-V-deficient mice but to a lesser extent than observed previously in sPLA₂-X-deficient mice. The most striking difference observed between the sPLA₂-V and sPLA₂-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA) in the sPLA₂-V^−/− mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V^−/− mice diminishes Th2 cytokine responses in the airways.

Conclusions

This paper illustrates the diverse roles of sPLA₂s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA₂-V as a potential new therapy to treat asthma and other allergic disorders.     

Effect of Exposure to Second-Hand Smoke on the Quality of Life: A Nationwide Population-Based Study from South Korea

Background

Although exposure to second-hand smoke (SHS) has been associated with various medical conditions, only limited data are available on its association with health-related quality of life (HRQOL), particularly data obtained with the EQ-5D or EQ visual analogue scale (VAS).

Methods

This cross-sectional study evaluated 10,532 adult never-smokers who participated in the fifth Korea National Health and Nutrition Examination Survey. By using linear regression models to adjust for possible confounders and incorporating survey weights in analyses, the association between exposure to SHS and HRQOL—measured with the EQ-5D index and the EQ-VAS score—was evaluated. Data were further stratified by the amount of exposure time.

Results

After weighted analysis and adjustment, exposure to SHS was significantly associated with lower measures on the EQ-5D index (β = −0.007, P = 0.005) and EQ-VAS score (β = −1.936, P < 0.001). When comparing the unexposed group with the groups exposed <2h/day and ≥2h/day, exposure to a longer duration of SHS was significantly associated with lower scores on the EQ-5D index and the EQ-VAS score.

Conclusion

In conclusion, exposure to SHS was associated with reduced HRQOL measured by the EQ-5D index and EQ-VAS score, revealing a dose-response relationship.     

Invasive Plants as Foci of Mosquito-Borne Pathogens: Red Cedar in the Southern Great Plains of the USA

EcoHealth - West Nile virus (WNV) is the most significant mosquito-borne disease affecting humans in the United States. Eastern redcedar (ERC) is a native encroaching plant in the southern Great...     

Level of Fatty Acid Binding Protein 5 (FABP5) Is Increased in Sputum of Allergic Asthmatics and Links to Airway Remodeling and Inflammation

BackgroundThe inflammatory processes in the upper and lower airways in allergic rhinitis and asthma are similar. Induced sputum and nasal lavage fluid provide a non-invasive way to examine proteins involved in airway inflammation in these conditions.ObjectivesWe conducted proteomic analyses of sputum and nasal lavage fluid samples to reveal differences in protein abundances and compositions between the asthma and rhinitis patients and to investigate potential underlying mechanisms.MethodsInduced sputum and nasal lavage fluid samples were collected from 172 subjects with 1) allergic rhinitis, 2) asthma combined with allergic rhinitis, 3) nonallergic rhinitis and 4) healthy controls. Proteome changes in 21 sputum samples were analysed with two-dimensional difference gel electrophoresis (2D-DIGE), and the found differentially regulated proteins identified with mass spectrometry. Immunological validation of identified proteins in the sputum and nasal lavage fluid samples was performed with Western blot and ELISA.ResultsAltogether 31 different proteins were identified in the sputum proteome analysis, most of these were found also in the nasal lavage fluid. Fatty acid binding protein 5 (FABP5) was up-regulated in the sputum of asthmatics. Immunological validation in the whole study population confirmed the higher abundance levels of FABP5 in asthmatic subjects in both the sputum and nasal lavage fluid samples. In addition, the vascular endothelial growth factor (VEGF) level was increased in the nasal lavage fluid of asthmatics and there were positive correlations between FABP5 and VEGF levels (r=0.660, p<0.001) and concentrations of FABP5 and cysteinyl leukotriene (CysLT) (r=0.535, p<0.001) in the nasal lavage fluid.ConclusionsFABP5 may contribute to the airway remodeling and inflammation in asthma by fine-tuning the levels of CysLTs, which induce VEGF production.     

TSG-6 Protein Is Crucial for the Development of Pulmonary Hyaluronan Deposition,Eosinophilia, and Airway Hyperresponsiveness in a Murine Model of Asthma

Hyaluronan (HA) deposition is often correlated with mucosal inflammatory responses, where HA mediates both protective and pathological responses. By modifying the HA matrix, Tnfip6 (TNF-α-induced protein-6; also known as TSG-6 (TNF-stimulated gene-6)) is thought to potentiate anti-inflammatory and anti-plasmin effects that are inhibitory to leukocyte extravasation. In this study, we examined the role of endogenous TSG-6 in the pathophysiological responses associated with acute allergic pulmonary inflammation. Compared with wild-type littermate controls, TSG-6^−/− mice exhibited attenuated inflammation marked by a significant decrease in pulmonary HA concentrations measured in the bronchoalveolar lavage and lung tissue. Interestingly, despite the equivalent induction of both humoral and cellular Th2 immunity and the comparable levels of cytokines and chemokines typically associated with eosinophilic pulmonary inflammation, airway eosinophilia was significantly decreased in TSG-6^−/− mice. Most importantly, contrary to their counterpart wild-type littermates, TSG-6^−/− mice were resistant to the induction of airway hyperresponsiveness and manifested improved lung mechanics in response to methacholine challenge. Our study demonstrates that endogenous TSG-6 is dispensable for the induction of Th2 immunity but is essential for the robust increase in pulmonary HA deposition, propagation of acute eosinophilic pulmonary inflammation, and development of airway hyperresponsiveness. Thus, TSG-6 is implicated in the experimental murine model of allergic pulmonary inflammation and is likely to contribute to the pathogenesis of asthma.     

Life Cycles and Emergence of Ephemeroptera and Plecoptera from Myrkdalsvatn,an Oligotrophic Lake in Western Norway

Comparative data are presented on nymphal growth and adult emergence for Nemoura avicularis, N. cinerea (Plecoptera), Siphlonurus aestivalis, S. lacustris and Leptophlebia vespertina (Ephemeroptera) from lake Myrkdalsvatn, western Norway. These species are all univoltine in Myrkdalsvatn. However, they show different nymphal growth patterns and emergence periods. The timing of emergence in Plecoptera was largely determined by water temperature, and in the Ephemeroptera by changes in both water temperature and cloud cover.     

The Microbial Community of the Cystic Fibrosis Airway Is Disrupted in Early Life

Background

Molecular techniques have uncovered vast numbers of organisms in the cystic fibrosis (CF) airways, the clinical significance of which is yet to be determined. The aim of this study was to describe and compare the microbial communities of the lower airway of clinically stable children with CF and children without CF.

Methods

Bronchoalveolar lavage (BAL) fluid and paired oropharyngeal swabs from clinically stable children with CF (n = 13) and BAL from children without CF (n = 9) were collected. DNA was isolated, the 16S rRNA regions amplified, fragmented, biotinylated and hybridised to a 16S rRNA microarray. Patient medical and demographic information was recorded and standard microbiological culture was performed.

Results

A diverse bacterial community was detected in the lower airways of children with CF and children without CF. The airway microbiome of clinically stable children with CF and children without CF were significantly different as measured by Shannon''s Diversity Indices (p = 0.001; t test) and Principle coordinate analysis (p = 0.01; Adonis test). Overall the CF airway microbial community was more variable and had a less even distribution than the microbial community in the airways of children without CF. We highlighted several bacteria of interest, particularly Prevotella veroralis, CW040 and a Corynebacterium, which were of significantly differential abundance between the CF and non-CF lower airways. Both Pseudomonas aeruginosa and Streptococcus pneumoniae culture abundance were found to be associated with CF airway microbial community structure. The CF upper and lower airways were found to have a broadly similar microbial milieu.

Conclusion

The microbial communities in the lower airways of stable children with CF and children without CF show significant differences in overall diversity. These discrepancies indicate a disruption of the airway microflora occurring early in life in children with CF.