Are there Risks from Nanocomposite Restoration Grinding for Dentists?

OBJECTIVES: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers. MATERIALS AND METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant´s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure. RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 µg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen. CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.

Single and multiple breath nitrogen washout compared with the methacholine test in patients with suspected asthma and normal spirometry.

BACKGROUND: Methods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N2SBW) and nitrogen multiple breath washout (N2MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N2SBW and N2MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in SIII at N2SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV1) in MCT. STUDY DESIGN AND METHODS: This prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N2SBW (SIII), N2MBW (Lung clearance index (LCI), Scond, Sacin), MCT (FEV1 and sGeff) as well as N2SBW between each methacholine dose. RESULTS: 182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N2SBW was pathological in 10.6% at baseline and N2MBW abnormality ranged widely (LCI 81%, Scond 18%, Sacin 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N2SBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with N2MBW. CONCLUSIONS: Both MCT and N2 washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.

Association of high-sensitivity CRP and FEV1%pred: a study on non-pulmonary disease in a population in Beijing, China.

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.

Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults.

INTRODUCTION: The genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin (HBA) restricts nitric oxide signalling in arterial endothelial cells via interactions with nitric oxide synthase; however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesised that an HBA gene deletion, common among Black individuals, would be associated with higher FeNO. METHODS: Healthy Black adults were enrolled at four study sites in North Carolina from 2005 to 2008. FeNO was measured in triplicate using a nitric oxide analyzer. The -3.7 kb HBA gene deletion was genotyped using droplet digital PCR on genomic DNA. The association of FeNO with HBA copy number was evaluated using multivariable linear regression employing a linear effect of HBA copy number and adjusting for age, sex and serum immunoglobulin-E levels. Post-hoc analysis employing a recessive mode of inheritance was performed. RESULTS: 895 individuals were in enrolled in the study and 720 consented for future genetic research; 643 had complete data and were included in this analysis. Median (25th, 75th) FeNO was 20 (13, 31) ppb. HBA genotypes were: 30 (4.7%) -a/-a, 197 (30.6%) -a/aa, 405 (63%) aa/aa and 8 (1.2%) aa/aaa. Subjects were 35% male with median age 20 (19, 22) years. Multivariable linear regression analysis revealed no association between FeNO and HBA copy number (ß=-0.005 (95% CI -0.042 to 0.033), p=0.81). In the post-hoc sensitivity analysis, homozygosity for the HBA gene deletion was associated with higher FeNO (ß=0.107 (95% CI 0.003 to 0.212); p=0.045). CONCLUSION: We found no association between HBA copy number and FeNO using a prespecified additive genetic model. However, a post hoc recessive genetic model found FeNO to be higher among subjects homozygous for the HBA deletion.

Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): protocol for an observational and translational pilot study.

INTRODUCTION: Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results. METHODS AND ANALYSIS: An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109/L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex-gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethics Committee of the CIUSSS de l'Estrie-CHUS, Sherbrooke, Quebec, Canada (#2023-4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05870215).

Association between serum uric acid/serum creatinine ratios and lung function in the general American population: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Assessment of lung function is essential for the early screening chronic airway diseases (CADs). Nevertheless, it is still not widely used for early diagnosing CADs in epidemiological or primary care settings. Thus, we used data from the US National Health and Nutrition Examination Survey (NHANES) to discuss the relationship between the serum uric acid/serum creatinine (SUA/SCr) ratio and lung function in general adults to gain the role of SUA/SCr in early assessment of lung function abnormalities. METHODS: From 2007 to 2012 NHANES, a total of 9569 people were included in our study. Using the regression model, XGBoost algorithm model, generalised linear model and two-piecewise linear regression model, the link between the SUA/SCr ratio and lung function was investigated. RESULTS: After correcting for confounding variables, the data revealed that forced vital capacity (FVC) declined by 47.630 and forced expiratory volume in one second (FEV1) decreased by 36.956 for each additional unit of SUA/SCr ratio. However, there was no association between SUA/SCr and FEV1/FVC. In the XGBoost model of FVC, the top five most important were glycohaemoglobin, total bilirubin, SUA/SCr, total cholesterol and aspartate aminotransferase, whereas in FEV1, were glycohaemoglobin, total bilirubin, total cholesterol, SUA/SCr and serum calcium. In addition, we determined the linear and inverse association between SUA/SCr ratio and FVC or FEV1 by constructing a smooth curve. CONCLUSIONS: In the general American population, the SUA/SCr ratio is inversely linked with FVC and FEV1, but not with FEV1/FVC, according to our research. Future studies should investigate the impact of SUA/SCr on lung function and identify possible mechanisms of action.

Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing.

To explore whether fractional exhaled nitric oxide (FeNO) non-suppression identifies corticosteroid resistance, we analysed inflammatory mediator changes during a FeNO suppression test with monitored high-intensity corticosteroid therapy. In linear mixed-effects models analysed over time, the 15 clinically distinct 'suppressors' (ie, ≥42% FeNO suppression) normalised Asthma Control Questionnaire scores (mean±SD, start to end of test: 2.8±1.4 to 1.4±0.9, p<0.0001) and sputum eosinophil counts (median (IQR), start to end of test: 29% (6%-41%) to 1% (1%-5%), p=0.0003) while significantly decreasing sputum prostaglandin D2 (254 (89-894) to 93 (49-209) pg/mL, p=0.004) and numerically decreasing other type-2 cytokine, chemokine and alarmin levels. In comparison, the 19 non-suppressors had persistent sputum eosinophilia (10% (1%-67%) despite high-intensity therapy) with raised end-test inflammatory mediator levels (1.9 (0.9-2.8)-fold greater than suppressors). FeNO non-suppression during monitored treatment implies biological corticosteroid resistance.

Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age.

BACKGROUND: Nitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX). METHODS: We followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models. RESULTS: eNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: -0.49, 95% CI -0.95 to -0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: -0.004, 95% CI -0.008 to -0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%-24% for every unit increase in eNO ppb. CONCLUSION: Higher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.

Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide.

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.

Eosinophilia and fractional exhaled nitric oxide levels in chronic obstructive lung disease.

INTRODUCTION: COPD is a heterogeneous disorder with varied phenotypes. We aimed to determine the prevalence of asthma history, peripheral eosinophilia and elevated FeNO levels along with the diagnostic utility of peripheral eosinophilia in identifying airway eosinophilic inflammation. METHODS: National Health and Nutrition Examination Survey data were analysed for the study period 2007-2010. Subjects aged ≥40 years with postbronchodilator FEV1/FVC ratio <0.70 were included. Receiver operator curve analysis was performed for sensitivity analysis. A p value of <0.001 is considered statistically significant. RESULTS: A total of 3 110 617 weighted COPD cases were identified; predominantly male (64.4%) and non-Hispanic whites (86.1%). Among our COPD subjects, 14.6% had a history of doctor diagnosed asthma, highest among females and other race Americans. The overall prevalence of peripheral eosinophilia is 36%, 38.3% among COPD subjects with asthma history, and 35.6% among COPD without asthma history. The overall prevalence of elevated FeNO ≥25 ppb is 14.3%; 28.7% among COPD subjects with asthma history and 13.0% among COPD without asthma history. DISCUSSION: The prevalence of FeNO levels ≥25 ppb and peripheral eosinophilia was significantly higher among COPD subjects with asthma compared with COPD without asthma history. Not all COPD subjects with peripheral eosinophilia and elevated FeNO levels have a reported history of asthma. Our study supports clinically phenotyping COPD subjects with eosinophilic inflammation be independent of their asthma history and peripheral eosinophilia can be used as a surrogate marker in resource-limited settings.

Trajectory of inhaled cadmium ultrafine particles in smokers.

INTRODUCTION: Tobacco smoking is a significant source of cadmium exposure among smokers. Most of inhaled heavy metals, including cadmium, are attached to ultrafine particles (UFPs) surface. A low inhaled UFP content in exhaled breath condensate reflects a high inflammatory status of airways. Increased respiratory epithelial permeability and translocation to the circulation is the proposed mechanism. UFP recovered from smokers' airways have high levels of cadmium compared with the airways of non-smokers. METHODS: Urine was collected from 22 smokers subjects and 43 non-smokers. Samples were analysed for UFP and cadmium content. UFP were measured in urine samples by means of the NanoSight LM20 system (NanoSight, UK). A Niton XL3 X-ray fluorescence spectrometer analyzer (Thermo Fischer Scientific, Germany) quantified heavy metal contents in the urine samples. RESULTS: Smokers had elevated UFP and cadmium content in urine compared with non-smokers (4.6 E8/mL and 20.6 ppm vs 3.4 E8/mL and 18.5 ppm, p=0.05 and p=0.05, respectively). Smokers had elevated levels of lead and rubidium compared with non-smokers (8.9 ppm and 27 ppm vs 7.8 ppm and 2 ppm, p=0.05 and p=0.04, respectively) DISCUSSION: We suggest that the trajectory of cadmium-related UFP in smokers begins by its inhalation into the airways. The UFPs induce inflammation and oxidative stress in the small airways, are subsequently translocated from the interstitium to the circulation and are finally detected and secreted in urine.

Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema.

Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 µm vs 291±36 µm); OR for emphysema per 10 µm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 µm vs 291 µm±26 µm); OR per 10 µm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.

Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases.

Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.

Novel non-invasive particles in exhaled air method to explore the lining fluid of small airways-a European population-based cohort study.

INTRODUCTION: Respiratory tract lining fluid of small airways mainly consists of surfactant that can be investigated by collection of the particles of exhaled aerosol (PExA) method. This offers an exciting prospect to monitor small airway pathology, including subjects with asthma and smokers. AIM: To explore the influence of anthropometric factors and gender on phospholipids, surfactant protein A (SP-A) and albumin of the lining fluid of small airwaysand to examine the association with asthma and smoking. Furthermore, to examine if the surfactant components can predict lung function in terms of spirometry variables. METHOD: This study employs the population-based cohort of the European Community Respiratory Health Survey III, including participants from Gothenburg city, Sweden (n=200). The PExA method enabled quantitative description and analytical analysis of phospholipids, SP-A and albumin of the lining fluid of small airways. RESULTS: Age was a significant predictor of the phospholipids. The components PC14:0/16:0, PC16:0/18:2 (PC, phosphatidylcholine) and SP-A were higher among subjects with asthma, whereas albumin was lower. Among smokers, there were higher levels particularly of di-palmitoyl-di-phosphatidyl-choline compared with non-smokers. Most phospholipids significantly predicted the spirometry variables. CONCLUSION: This non-invasive PExA method appears to have great potential to explore the role of lipids and proteins of surfactant in respiratory disease.

Use of exhaled breath condensate (EBC) in the diagnosis of SARS-COV-2 (COVID-19).

False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.

Ambient air pollution is associated with airway inflammation in older women: a nested cross-sectional analysis.

BACKGROUND: Air pollution is a risk factor for chronic obstructive pulmonary disease (COPD). Fraction of exhaled nitric oxide (FeNO) could be a useful biomarker for health effects of air pollutants. However, there were limited data from older populations with higher prevalence of COPD and other inflammatory conditions. METHODS: We obtained data from the German Study on the influence of Air pollution on Lung function, Inflammation and Ageing. Spirometry and FeNO were measured by standard techniques. Air pollutant exposures were estimated following the European Study of Cohorts for Air Pollution Effects protocols, and ozone (O3) measured at the closest ground level monitoring station. Multiple linear regression models were fitted to FeNO with each pollutant separately and adjusted for potential confounders. RESULTS: In 236 women (mean age 74.6 years), geometric mean FeNO was 15.2ppb. Almost a third (n=71, 30.1%) of the women had some chronic inflammatory respiratory condition. A higher FeNO concentration was associated with exposures to fine particles (PM2.5), PM2.5absorbance and respirable particles (PM10). There were no significant associations with PMcoarse, NO2, NOx, O3 or length of major roads within a 1 km buffer. Restricting the analysis to participants with a chronic inflammatory respiratory condition, with or without impaired lung function produced similar findings. Adjusting for diabetes did not materially alter the findings. There were no significant interactions between individual pollutants and asthma or current smoking. CONCLUSIONS: This study adds to the evidence to reduce ambient PM2.5 concentrations as low as possible to protect the health of the general population.

Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations.

BACKGROUND: Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated particularly with the risk of exacerbations. We evaluated the relationship of BEC and FeNO as complementary and independent biomarkers of severe asthma exacerbations. METHODS: This observational study included data from the Optimum Patient Care Research Database. Asthma patients (18-80 years) with valid continuous data for 1 year before FeNO reading, ≥ 1 inhaled corticosteroid prescription, and BEC recorded ≤ 5 years before FeNO reading were separated into cohorts. Categorisation 1 was based on the American Thoracic Society criteria for elevated FeNO concentration (high: ≥ 50 ppb; non-high: < 25 ppb) and BEC (high: ≥ 0.300 × 109 cells/L; non-high: < 0.300 × 109 cells/L). Categorisation 2 (FeNO concentration, high: ≥ 35 ppb; non-high: < 35 ppb) was based on prior research. Reference groups included patients with neither biomarker raised. RESULTS: In categorisation 1, patients with either high FeNO or high BEC (n = 200) had a numerically greater exacerbation rate (unadjusted rate ratio, 1.31 [95% confidence interval: 0.97, 1.76]) compared with patients in the reference group. Combination of high FeNO and high BEC (n = 27) resulted in a significantly greater exacerbation rate (3.67 [1.49, 9.04]). Similarly, for categorisation 2, when both biomarkers were raised (n = 53), a significantly greater exacerbation rate was observed (1.72 [1.00, 2.93]). CONCLUSION: The combination of high FeNO and high BEC was associated with significantly increased severe exacerbation rates in the year preceding FeNO reading, suggesting that combining FeNO and BEC measurements in primary care may identify asthma patients at risk of exacerbations.

Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis.

BACKGROUND: Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes. OBJECTIVE: To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults. DATA SOURCES: Cochrane reviews with standardised searches up to February 2017. STUDY SELECTION: The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow). RESULTS: The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function. CONCLUSION: Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function.

The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis.

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.