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Background: Small airway dysfunction (SAD) is increasingly recognized as an important feature of pediatric asthma yet typically relies on spirometry-derived FEF 25-75 to detect its presence. Multiple breath washout (MBW) and oscillometry potentially offer improved sensitivity for SAD detection, but their utility in comparison to FEF 25-75 , and correlations with clinical outcomes remains unclear for school-age asthma. We investigated SAD occurrence using these techniques, between-test correlation and links to clinical outcomes in 57 asthmatic children aged 8-18 years., Methods: MBW and spirometry abnormality were defined as z -scores above/below ± 1.96, generating MBW reference equations from contemporaneous controls ( n  = 69). Abnormal oscillometry was defined as > 97.5 th percentile, also from contemporaneous controls ( n  = 146). Individuals with abnormal FEF 25-75 , MBW, or oscillometry were considered to have SAD., Results: Using these limits of normal, SAD was present on oscillometry in 63% (resistance at 5-20 Hz; R5-R20; >97.5 th percentile), on MBW in 54% (S cond ; z -scores> +1.96) and in spirometry FEF 25-75 in 44% of participants ( z -scores< -1.96). SAD, defined by oscillometry and/or MBW abnormality, occurred in 77%. Among those with abnormal R5-R20, S cond was abnormal in 71%. Correlations indicated both R5-R20 and S cond were linked to asthma medication burden, baseline FEV 1 and reversibility. Additionally, S cond correlated with F E NO and magnitude of bronchial hyper-responsiveness. SAD, detected by oscillometry and/or MBW, occurred in almost 80% of school-aged asthmatic children, surpassing FEF 25-75 detection rates., Conclusions: Discordant oscillometry and MBW abnormality suggests they reflect different aspects of SAD, serving as complementary tools. Key asthma clinical features, like reversibility, had stronger correlation with MBW-derived S cond than oscillometry-derived R5-R20.

We studied associations between fractional exhaled nitric oxide (FeNO), health and household exposure among school children (N = 348) in Penang, Malaysia. Multiple logistic regression and linear mixed models were applied. Overall, 46.0% had elevated FeNO (>20 ppb) and 10.6% diagnosed asthma. Male gender (p = 0.002), parental asthma or allergy (p = 0.047), cat allergy (p = 0.009) and seafood allergy (p < 0.001), diagnosed asthma (p = 0.001), wheeze (p = 0.001), ocular symptoms (p = 0.001), rhinitis (p = 0.002) and respiratory infections (p = 0.004) were all associated with FeNO. Students exposed to ETS had lower FeNO (p = 0.05). Dampness and mould was associated with wheeze (p = 0.038), especially in wooden homes (interaction p = 0.042) and among students with elevated FeNO (interaction p = 0.024). Cat keeping increased rhinitis (p = 0.041) and respiratory infections (p = 0.008) and modified the dampness associations. In conclusion, FeNO can be associated with ocular and respiratory symptoms. Elevated FeNO, cat keeping and a wooden house can enhance the risk of wheeze when exposed to dampness and mould.

Background: In asthma, suppression of fractional exhaled nitric oxide (FENO) is a marker of adherence in the short-term. The usefulness of FENO to indicate change in adherence in the longer term is unknown. The aims of this study were to determine the relationship between changes in adherence and corresponding changes in FENO over short (1 week) and long-term (3 month) periods., Methods: After establishing initial ICS adherence using electronic inhaler monitor (EIM) devices, reminders were switched on for 1 week ('short-term') to optimize adherence. Reminders were then switched off and patients followed up after 3 months ('long-term'). FENO was measured at the start and end of each period. Using linear regression, we analyzed change in FENO in relation to change in adherence., Results: Forty-two patients contributed complete data for analysis. In the short-term, change in adherence was independently associated with change in FENO ( β = -0.36, p  = 0.036) even after adjusting for initial adherence and ICS dose. The higher the initial FENO, the greater the decline in FENO with improved adherence. This relationship between change in adherence and change in FENO was not observed in the long-term., Conclusion: Change in adherence over 1 week following the use of EIM reminders independently predicted change in FENO. This relationship was not maintained at 3 months.

Objective: Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma., Methods: A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models., Results: A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (β = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (β = 16.1, 95% CI: 1.5 to 30.8)., Conclusions: Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children.

Objective: Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g. inhaled (ICS)/oral corticosteroid (OCS) use. We hypothesized that body mass index (BMI) would affect T2-biomarker levels, after adjusting for covariates., Methods: A retrospective analysis of data from two recent local trials of 153 participants with asthma (102 difficult-to-treat, 51 mild). Measurements included BMI, fractional exhaled nitric oxide (FeNO) and eosinophils. Correlation and regression analysis were performed for each biomarker to describe their relationship with BMI. Data was analyzed overall, and by asthma severity, T2-status and BMI tertile., Results: Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25 ppb lowest tertile, 18 ppb highest tertile; p  = 0.014). Spearmans rank showed a negative correlation between BMI and FeNO in difficult-to-treat asthma (ρ= -0.309, p  = 0.002). Linear regression adjusting for sex, age, smoking, atopy, allergic/perennial rhinitis, ICS and OCS confirmed BMI as a predictor of FeNO overall (β= -2.848, p  = 0.019). Eosinophils were reduced in the highest BMI tertile versus lowest in difficult-to-treat asthma (0.2x10 9 /L, 0.3x10 9 /L respectively; p  = 0.02)., Conclusions: Increasing BMI is associated with lower FeNO in asthma when adjusted for relevant covariates, including steroid use. There also appears to be an effect on eosinophil levels. Obesity, therefore, affects T2 biomarker levels with implications for disease endotyping and determination of eligibility for biologic therapy. Whether this is due to masking of underlying T2-high status or development of a truly T2-low endotype requires further research.

Asthma is a fairly common health problem for pregnant women and a potentially serious medical condition that may complicate pregnancy. Most complications are related to lack of disease control, which can adversely affect both maternal quality of life and perinatal outcomes. In this article, we review recent literature concerning asthma in pregnancy, describing the course of the disease and associated complications. Furthermore, we review and discuss asthma monitoring and management during pregnancy, labor and post-partum. The course of asthma symptoms during pregnancy is unpredictable but exacerbations are more common during the second trimester. The causes are multifactorial and asthma phenotype may have a role. It has been proposed that combined use of CARAT (Control of Allergic Rhinitis and Asthma Test) and lung function tests can be used to monitor and adjust therapy during pregnancy in patients with asthma. As a complement, an approach that considers airway inflammation assessment using fractional exhaled nitric oxide (FeNO), a noninvasive marker of inflammation, may improve asthma control during pregnancy. It is important to consider a few but relevant differences in asthma management and treatment regarding pregnancy and the peri-partum period to safely achieve optimal management of asthma during all these phases for both mother and offsprings.

Objective: There are few studies on fractional exhaled nitric oxide (FeNO) among children in subtropical areas. We studied associations between FeNO and respiratory symptoms, reported diagnosed allergies and indoor and outdoor environmental factors in first grade junior high school students ( N  = 270) in upper northern Thailand., Methods: Data on demographics, health and home environment were collected by a questionnaire distributed in dry season (February-March 2018). FeNO was measured when the research team visited the school. Daily outdoor pollution data (PM 10 and ozone) were collected from the nearest monitoring station 3 days (lag 3) and 7 days (lag 7) before the FeNO measurements. Two-level (student, school) linear mixed models were used to analyze associations, adjusting for gender and family education level., Results: In total, 29.6% had elevated FeNO level (>20 ppb) and 7.8% reported any allergy diagnosed by a doctor. Male gender ( p  = 0.02), diagnosed allergy ( p  = 0.001), especially to cat ( p  = 0.001) and house dust mite (HDM) allergies ( p  = 0.001) were associated with FeNO. Eye symptoms ( p  = 0.01), rhinitis symptoms ( p  = 0.03) and dyspnea ( p  = 0.05) in the last 3 days were associated with FeNO. Household indoor mold ( p  = 0.03), gas cooking ( p  = 0.03) and PM 10 (lag 3 and lag 7) were negatively (protective) associated with FeNO., Conclusions: Diagnosed allergy, especially to cat and HDM, can be associated with increased FeNO. Indoor mold and gas cooking can be associated with lower FeNO. Ocular, nasal and dyspnea symptoms reported by students in dry season in northern Thailand can be associated with FeNO, a biomarker of Th2 driven airway inflammation.

Objective: Exposure to cigarette smoke complicates the treatment and management of asthma through a variety of inflammatory effects. This study aimed to investigate the differences between newly diagnosed cases of asthma in smokers and nonsmokers in terms of localized and systemic biomarkers following treatment with inhaled corticosteroids (ICS) or ICS in combination with a long-acting β2 agonist (LABA)., Methods: Specimens of exhaled breath condensate (EBC) from newly diagnosed patients with asthma were used to quantify inflammation in the airways, while blood samples were used to assess systemic inflammation. In both samples, the levels of IL-6, LTB4, LTD4, and 8-isoprostane were measured and these were repeated after 3 months of treatment with ICS or ICS + LABA., Results: Of the 20 patients, 10 (50%) were nonsmokers with asthma (NSA) and 10 (50%) smokers with asthma (SA). There was no statistically significant difference in the blood or EBC levels of IL-6, LTB4, LTD4, or 8-isoprostane between the groups prior to treatment. Only the decrease in 8-isoprostane level in the EBC samples was found to be significantly greater in the NSA group after treatment (for smokers, the change was 2.91 ± 23.22, while for nonsmokers it was -22.72 ± 33.12, p  = 0.022). Post-treatment asthma control was significantly better in the NSA group ( p  = 0.033)., Conclusion: Monitoring the alterations in 8-isoprostane levels in EBC in patients with asthma who smoke may be helpful in deciding on therapeutic management and switching treatments. Asthma control was better in nonsmokers than in smokers.

Background. Chronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures. Fractional exhaled nitric oxide (FeNO) has been considered a useful biomarker for predicting inhaled corticosteroids (ICS) response. We evaluated the relationship between FeNO and ICS response in chronic cough by performing a systematic review with meta-analysis. Methods. PubMed, Web of Science, Scopus and EMBASE databases were systematically searched. Differences were expressed as Odds Ratio (OR) with 95% confidence intervals (95%CI). Pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and area under the hierarchical summary receiver operating characteristic curve (HSROC AUC ) were estimated. Results. Nine articles on 740 chronic-cough patients showed that the response rate to ICS was 87.4% (95%CI: 83.8-91.0) in 317 patients with a high FeNO and 46.3% (95%CI: 41.6-51.0) in 423 controls, with an attributable proportion of 47.0% and a diagnostic OR of 9.1 (95%CI: 3.7-22.4, p  < .001). The pooled estimate of diagnostic indexes resulted in a sensitivity of 68.5% (95%CI: 46.7-84.4) and specificity of 81.9% (95%CI: 63.0-92.3), with a HSROC AUC of 0.82 (95%CI: 0.64-0.90). In a realistic scenario with a pre-test probability set at 30%, based on a pooled PLR of 3.79 (95%CI: 1.24-7.47) and NLR of 0.38 (95%CI: 0.22-0.66), the post-test probability was 62% with a high FeNO and 14% if the test was negative. Subgroup analyses confirmed a better performance for the recommended FeNO cut-off greater than 25 ppb. Meta-regression and sensitivity analyses showed no impact of major demographic and clinic variables on results. Conclusions. A high FeNO before starting ICS therapy may help identify chronic-cough patients responding to treatment, with a better performance ofhigher cut-off values. Further studies are needed to evaluate the real usefulness of this biomarker to guide cough therapy and optimise strategies in different healthcare settings (community, hospital, rehabilitation).Key messagesChronic cough is a disabling condition with a high proportion of diagnostic and therapeutic failures.Fractional exhaled nitric oxide (FeNO) may be a useful biomarker for identifying chronic cough patients who respond to steroid treatment.A FeNO cut-off lower than 25 ppb should be considered irrelevant for this clinical application.

Introduction: Lung cancer remains the most prevalent cause of cancer mortality worldwide mainly due to insufficient availability of early screening methods for wide-scale application. Exhaled breath condensate (EBC) is currently considered as one of the promising targets for early screening and is particularly attractive due to its absolutely noninvasive collection and possibility for long-term frozen storage. EBC proteome analysis can provide valuable information about the (patho)physiological changes in the respiratory system and may help to identify in time a high risk of lung cancer. Mass spectrometry (MS) profiling of EBC proteome seems to have no alternative in obtaining the most extensive data and characteristic marker panels for screening., Areas Covered: This special report summarizes the data of several proteomic studies of EBC in normal and lung cancer (from 2012 to 2021, PubMed), focuses on the possible reasons for the significant discrepancy in the results, and discusses some aspects for special attention in further studies., Expert Opinion: The significant discrepancy in the results of various studies primarily highlights the need to create standardized protocols for the collection and preparation of EBC for proteomic analysis. The application of quantitative and targeted LC-MS/MS based approaches seems to be the most promising in further EBC proteomic studies.

Objectives: Herpes virus entry mediator (HVEM) is a costimulatory molecule, and has been proved to play an important role in airway inflammatory and remodeling processes of asthma. We aimed to investigate the expression of HVEM gene in patients with asthma as a means of assessing disease severity. Methods: This study was carried out on 59 subjects, 16 patients with mild persistent asthma, 11 patients with moderate persistent asthma, 13 patients with severe persistent asthma, and 19 age and gender matched healthy controls. The HVEM mRNA expressions of all subjects were determined by real time PCR. Correlations between HVEM mRNA expression and fractional exhaled nitric oxide (FeNO), pulmonary function test values, total blood white cell count and differential, total immunoglobulin E (IgE) level, and Asthma Control Test (ACT) score were analyzed, respectively. The discrimination abilities of HVEM mRNA between different groups were tested using receiver operating characteristics (ROC) curve analyses. Results: This study showed the expressions of HVEM mRNA were significantly higher in the patients with severe and moderate persistent asthma than in patients with mild persistent asthma and healthy subjects (2.97 ± 1.23 vs. 1.17 ± 0.42 vs. 0.62 ± 0.38 vs. 0.46 ± 0.18/NAPDH, p  < 0.001), but there was no significant difference between patients with mild persistent asthma and health controls (0.62 ± 0.38 vs. 0.46 ± 0.18/NAPDH, p  = 0.557). HVEM mRNA expression at cut off point [1.01/NAPDH, area under the ROC curve (AUC) = 0.99] is sufficient to discriminate severe patients from mild-to-moderate patients, and at cut off point (0.93/NAPDH, AUC = 0.91) for discrimination of moderate-to-severe patients from mild ones, while at cut off point (0.76/NAPDH, AUC = 0.75) for discrimination of asthmatic patients from controls. Furthermore, HVEM mRNA expression was positively correlated with FeNO level ( r  = 0.524, p  = 0.015), and total lymphocyte count ( r  = 0.426, p  = 0.017) in patients with persistent asthma. Conclusions: HVEM gene expressions can be used as a potential biomarker for evaluating the severity of patients with persistent asthma.

Background: A subset of chronic pancreatitis patients respond poorly to pancreatic enzyme replacement therapy. Small intestinal bacterial overgrowth (SIBO) is considered to be one of the major reasons for this poor response. Previous studies have reported a wide range of prevalence of SIBO in patients with chronic pancreatitis. We aimed to assess the prevalence of SIBO in chronic pancreatitis using quantitative jejunal aspirate culture and glucose hydrogen breath test (GHBT). The sensitivity and specificity of GHBT for the diagnosis of SIBO in chronic pancreatitis were also estimated., Methods: Newly diagnosed chronic pancreatitis patients were recruited into the study. A detailed history and relevant laboratory tests were done. All patients underwent an endoscopy and jejunal fluid aspiration for bacterial cultures and GHBT to detect SIBO. The results of GHBT were compared with jejunal fluid aspirate culture., Results: The jejunal aspirate culture was positive in 18/48 (37.5%) patients while the GHBT showed that 14/48 (29%) patients had SIBO. The sensitivity, specificity, positive and negative predictive value of GHBT in our study was 44.4, 80, 57.14 and 70.59%, respectively., Conclusions: SIBO is not uncommon in chronic pancreatitis patients. One-third of our study population had SIBO. GHBT has low sensitivity but had high specificity in the diagnosis of SIBO in chronic pancreatitis.

Objective: Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease., Methods: EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls., Results: EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls., Conclusions: In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

Objective: Pulmonary function and airway inflammation were investigated in stable pre- to late-adolescent asthmatics without long-term control medications and compared with those in currently medicated asthmatics. Methods: Subjects comprised 34 well-controlled asthmatic children (aged 8.1-18.0 years; group without medication). Flow volume curves before and after inhaling a β2 agonist, a bronchodilator (BD), were compared and fractional exhaled nitric oxide (FENO) concentrations were measured. All patients were attack-free for at least 12 months prior to testing without the use of asthma medications for at least three months. Fifty-one age-matched stable asthmatics with medications at the time of the present study (group with current medication) underwent the same examinations. Results: The rate of children whose respiratory function after BD improved by 20% or more in both the central and peripheral airways (High responder at total airways subtype: HTA) was significantly higher in the group without medication than in that with current medication (17.6 and 2.0%, respectively; p  < 0.01). Furthermore, FEV 1.0 % pred after BD was significantly lower for HTA than for the low responder subtype in the same group (94.8 ± 3.5 and 104.1 ± 1.5% respectively, p  < 0.05). FENO concentrations in the group without medication were high, but not significantly different from those in the group with current medication. Conclusions: Stable asthmatic children without medication include a certain percentage of those with irreversible airflow limitation possibly due to airway remodeling. The control of daily asthma symptoms with long-term control medications may effectively prevent airway remodeling.

Background: Asthma is characterized by airway inflammation, variable airflow obstruction, and airway hyperresponsiveness (AHR). Generally, AHR takes longer to resolve than does airflow obstruction or clinical symptoms. AHR occasionally persists despite adequate asthma treatment. Objective: To evaluate factors which associates with residual AHR in patients with seemingly remitted airway inflammation. Methods: Patients who exhibited high fractional exhaled nitric oxide (FeNO) levels (>25 ppb) at the first visit (Visit 1) and normalized FeNO levels (<25 ppb) after adequate asthma treatment, including inhaled corticosteroid administration (Visit 2), were analyzed. Patients underwent a blood test, FeNO and small airway/alveolar nitric oxide concentration (CANO) measurements and a methacholine challenge test (continuous inhalation method) at both visits. Clinical indices were compared between patients with and without residual AHR. Results: Fifty patients were analyzed. All exhibited high FeNO levels at Visit 1 [mean, 54.0 ppb (95% confidence interval, 42.4-65.5)] and improvement of FeNO levels at Visit 2 [20.4 (19.2-21.6)] ( p  < 0.0001). Thirty-three patients (66%) had remission of AHR at Visit 2. No significant differences were observed between patients with and without residual AHR in terms of FeNO levels, lung function parameters and blood eosinophil counts at both visits. CANO level at Visit 2 was the only factor that significantly differed between patients with residual AHR [2.7 (1.9-3.6)] and those who achieved AHR remission [0.8 (0.5-1.0)] ( p  < 0.0001). Conclusion: Small airway inflammation, as assessed by CANO, was associated with residual AHR in patients with Th2-high asthma.

Background : Almost one third of the world population suffers from allergic conditions. Respiratory symptoms are common in Malaysian children but there are few studies on fractional exhaled nitric oxide (FeNO), inclusive of field clinical test for asthma among children in Malaysia. The aim was to provide insight on factors related to level of FeNO among students in Terengganu, Malaysia. Methods : In total, 487 randomly selected students from eight secondary schools participated (13-14 years old). A Standardized questionnaire was used to obtained information on doctors' diagnosed asthma, current asthma and respiratory symptoms. FeNO measurement and skin prick test (SPT to common allergen) were conducted. Results : The geometric mean FeNO was 16.7 ppb. Totally, 38.4% of students had elevated FeNO level (>20 ppb) and 40.3% had had positive SPT to house dust mites allergens (HDM), Dermatophagoides pteronyssinus (Der p 1), Dermatophagoides farinae (Der f 1) or Felis domisticus (cat). Male gender, height, parental history of allergy, self-reported allergy, and atopy were associated with FeNO. In particular, a combination of sensitization to HDM or cat and elevated FeNO were associated with doctor-diagnosed asthma and self-reported allergy to food, pollen and cat. Conclusion : Asthma, respiratory symptoms and sensitization to HDM and cat are common among students and presence of elevated FeNO levels indicate ongoing airway inflammation.

We studied whether fractional exhaled nitric oxide ( F ENO ) can differentiate chronic obstructive pulmonary disease (COPD) with concurrent diagnosis of asthma from COPD-only as well as its ability to predict disease severity and progression. This study was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Subjects of ≥40 years old completed F ENO measurements were subdivided into four groups, including COPD ( N  = 86 [COPD-only ( N  = 35) and COPD with concurrent diagnosis of asthma ( N  = 51)], healthy ( N  = 72), and at risk ( N  = 151). Three of the most common clinical definitions were used for characterizing COPD with concurrent diagnosis of asthma: 1) atopy and self-reported physician diagnosis of asthma, 2) ≥12% and ≥200 ml post-bronchodilator FEV1; 3) self-reported physician diagnosis of asthma. F ENO values were classified using quartiles and the American Thoracic Society (ATS) guideline 2011. Compared to COPD-only, more COPD with concurrent diagnosis of asthma had a significant F ENO50 level of [Formula: see text] 33.5 ppb (fourth quartile) than COPD-only ( p  = 0.045, 0.011, and 0.006, for definition 1, 2, and 3, respectively). Considering the ATS guideline 2011, fewer COPD with concurrent diagnosis of asthma had F ENO50 < 25 than COPD-only, which was statistically significant with definition 1 and 3 ( p  = 0.038 and 0.026, respectively). F ENO as a biomarker has the potential to be used as a complementary value for differentiating COPD with concurrent diagnosis of asthma from COPD-only. Further studies should be conducted on validated definitions of COPD with concurrent diagnosis of asthma, which may include a reference to the type of airway inflammation in addition to the clinical definition.

Background: The mannitol test is widely used for assessment of airway responsiveness in patients with possible asthma, but our knowledge of the value in everyday clinical practice is limited. Objective: To investigate the diagnostic value of the mannitol test in a clinical setting. Methods: All patients having a mannitol challenge test as part of their diagnostic work-up for asthma at the respiratory outpatient clinic, Hvidovre Hospital, over a 5-year period were included in the present analysis. Case history, including previous diagnoses, spirometry, exhaled nitric oxide (F E NO) was obtained. The mannitol challenge was performed according to guidelines, i.e. increasing doses of mannitol (from 5 to 635 mg) until maximum dose or a 15% decline in FEV 1 (PD 15 ) was achieved (positive test defined as a PD 15 < 635 mg). Results: Our cohort comprised 566 patients (210 men). Post-challenge, 247 patients were diagnosed with asthma by a specialist in respiratory medicine, of whom 138 (56%) had a positive mannitol test. A diagnosis of asthma was ruled out by the specialist in 319 individuals, of whom 18 (6%) had a positive mannitol test and 77 (24%) previous doctor-diagnosed asthma (but with no evidence of a confirmatory test). The specificity and sensitivity of the test was 94% and 56%, respectively. Female gender ( p  = 0.005), increasing BMI ( p  < 0.001), exercise-induced cough ( p  = 0.002), night-time respiratory symptoms ( p  = 0.002), low FEV 1 /FVC ratio ( p  = 0.008) and high F E NO ( p  < 0.001) were determinants for a positive mannitol test. Conclusion: In everyday clinical work-up of patients with possible asthma, the sensitivity and specificity of the mannitol challenge test is comparable to previous controlled trials.

Objectives: Although Helicobacter pylori ( H . pylori ) infection is one of the most important risk factors for gastric cancer, the molecular mechanisms underlying the progression of H . pylori -induced gastric cancer remain unclear. Previous studies have demonstrated that Integrin-associated protein (CD47) plays an important role in the development of gastric cancer. Hence, the aim of this study was to preliminarily explore the relationship between CD47 and H. pylori infection. Methods: A total of 417 adults who underwent health checkups at a hospital were recruited in 2018. Serum levels of CD47 and tumor necrosis factor-α (TNF-α) were determined using an enzyme-linked immunosorbent assay. 13 C urea breath test ( 13 C-UBT) was carried out to diagnose H . pylori infection in all participants. Results: Compared with H. pylori -negative participants, H. pylori -positive participants have higher levels of serum CD47 and TNF-α. H. pylori infection, the levels of serum TNF-α and low density lipoprotein (LDL) are the independent predictors of serum level of CD47 in adults. In addition, a potential diagnostic value of serum CD47 level for H. pylori infection has been demonstrated in our study. Conclusion: H. pylori infection is closely associated with the serum level of CD47 in adults, suggesting that H . pylori may promote gastric cancer progression by activating CD47-mediated oncogenic pathways.

Objective: Τo investigate the effect of an asthma care educational program for children and adolescents with asthma, on adherence to asthma control treatment and on clinical indices. Methods: Individuals newly diagnosed with asthma, aged 4-16 years, randomized to the intervention and control group. The participants were monitored for 6 weeks. At baseline, before the initiation of inhaled corticosteroids/long-acting beta 2 -agonist (ICS/LABA), the intervention group attended the educational program; the control group received the usual care. Both groups were equipped with electronic monitoring devices for measuring adherence. Spirometry, exhaled nitric oxide fraction (FeNO), and asthma control test (ACT) score were measured in both groups in the pre and post-ICS/LABA initiation visit. Results: Seventy-eight participants were enrolled in this study ( n  = 39 to each group). Median percentage of adherence was 73% for the total sample, and 80% and 68% in intervention and control group, respectively ( p  < 0.001). In multivariate analysis, the program was positively associated with improved adherence ( p  < 0.001). ICS/LABA had a positive effect on spirometric indices, FeNO, and ACT score, whilst the educational program did not improved significantly the above variables. Conclusions: Establishing and increasing adherence is challenging. An asthma care educational program is associated with greater short-term adherence during a period of active monitoring.

The value of fractional exhaled nitric oxide (FeNO) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to assess whether FeNO is a more valuable biomarker than blood eosinophil count for identifying clinical characteristics of COPD. Stable COPD patients ( n  = 390) were included and stratified by FeNO and blood eosinophil counts at recruitment. The demographic characteristics, lung functions, St George Respiratory Questionnaire (SGRQ), serum inhaled allergen-specific IgE and the exacerbations in the preceding 12 months were compared. Risk factors for moderate or severe exacerbation in the preceding 12 months were examined by binary regression analysis. The cross-sectional study showed that 167 patients had high level of FeNO (≥25 ppb) and 223 in low level (<25 ppb), while 138 patients had high blood eosinophil count (≥200 cells/μL) and 252 had low (<200 cells/μL). Compared with the high FeNO group, there were higher proportion of patients with GOLD III-IV, higher SGRQ scores, more exacerbations in the preceding 12 months, and with lower positive proportion of sIgE in the low FeNO group ( p  < 0.05 for all). However, these phenomena above were not associated with blood eosinophil count. Finally, high FeNO level was associated with a lower moderate or severe exacerbation in preceding 12 months (RR: 0.541 [95%CI 0.319-0.917], p  = 0.023). In stable COPD patients, FeNO, but not blood eosinophil count was associated with the COPD severity and allergic airway inflammation. However, the role of FeNO in guiding personalized treatment of COPD patients need to be further investigated.

Introduction: Breath analyzers are commonly used to test for alcohol intoxication, i.e., elevated systemic levels of ethanol, at workplaces and among vehicle drivers. However, local low-dose exposure to ethanol in the mouth or airways may temporarily increase the breath-alcohol concentration (BrAC) without the systemic ethanol level being affected, leading to false positive test results. The aim of this study was to assess the impact of local ethanol exposure on the BrAC. Methods: Eleven healthy adults (six women) were exposed to on average 856 mg/m 3 ethanol vapor for 15 min, followed by repeat collection of exhaled breath in Tedlar bags. One hour later, the subjects washed their mouth for 30 s with a typical mouthwash containing 22% ethanol and post-exposure breaths were again collected repeatedly. Negligible systemic uptake of ethanol was confirmed by analysis of blood sampled before, between and after the exposures. Ethanol in breath and blood was analyzed by gas chromatography. Results: No or very low levels (less than 0.002 mg/g) of ethanol were detected in blood at any time point, indicating negligible systemic uptake. The decline in breath was mono-exponential after both exposures with average half times of 0.4 (range 0.3-0.8) min after inhalation exposure and 1.9 (1.1-3.0) min after mouthwash. BrAC levels in the first sample, collected a few seconds after exposure, were 0.14 (0.07-0.13) mg/L after inhalation and 4.4 (2.7-6.0) mg/L after mouth wash. On average, it took 0.5 (0.06-0.7) min and 11 (6-15) min, respectively, for the BrAC to fall below the Swedish statutory limit of 0.1 mg/L air. Conclusion: In practice, use of breath analysis should not be a problem even if the subject inhaled ethanol vapors before the test. In contrast, use of ethanol-containing mouthwash results in a false positive test if sampling is done within 15 min.

Objectives: The study aims to investigate occupational exposure to carbon fibers impregnated with epoxy resins (carbon fiber reinforced [CFR]) in workers at an airplane fuselage section construction plant, by environmental and biological monitoring. Materials and methods: Determination of airborne CFR was done by environmental sampling with active samplers, 11 of which were stationary and 19 personal samplings. The subsequent analyses were performed in the scanning electron microscope fitted with an X-ray microanalysis system (SEM-EDXA). Biological monitoring was carried out by determining CFR in exhaled breath condensate (EBC) collected from 19 male workers who wore personal environmental samplers (exposed workers) and from 10 male workers at the same factory who had no occupational exposure to CFR (internal controls). CFR analysis was done by SEM, applying the method used for determining asbestos fibers in aqueous samples. Results: The airborne CFR concentrations were found to be significantly higher ( p  = 0.03) at personal samplings (median value 7.01 ff/L, range 1.24-11.16 ff/L) than stationary samplings (median value 1.93 ff/L, range 0.55-10.09 ff/L). The aerodynamic diameters calculated starting from the length and geometric diameter of the sampled CFRs were always higher than 20 µm. CFR was not found in any of the EBC samples collected from the exposed workers and controls. Conclusions: Despite the evidence of occupational exposure to low concentrations of CFR, the absence of such fibers in the EBC in the exposed workers confirms their non-respirability, as expected based on their aerodynamic diameter.

Many patients with chronic obstructive lung disease (COPD) experience exacerbations. The diagnosis of an exacerbation is solely based on symptoms. We hypothesized that exhaled breath profiles, measured by Gas Chromatography-Mass Spectrometry (GC-MS) or electronic nose (eNose), are different between stable disease and exacerbations and may have the potential to serve as biomarkers for COPD exacerbations. In this prospective follow-up study, breath samples were taken during stable COPD, during a subsequent exacerbation and after recovery. Samples were analyzed by GC-MS and eNose. CCQ symptom scores were associated with univariate outcomes of GC-MS and eNose using analysis of covariance (ANCOVA). After multivariate modeling by Principal Component Analysis (PCA), paired student t -tests were performed. Sixty-eight patients were included, 31 had an exacerbation and 16 patients had breath sampled at all three time points. Significant differences were found in breathprints taken during exacerbation as compared to baseline and recovery for both GC-MS and eNose. Breath profiles obtained by GC-MS as well as by eNose showed a correct classification of 71% (10/14) for baseline vs exacerbation and of 78% (11/14) for exacerbation vs recovery. These results provide proof of principle that exhaled breath can serve as a noninvasive biomarker for the diagnosis of COPD exacerbations.

A novel doubly [1- 13 C, α- 15 NH 2 ]-labelled amino acid method (DLAAM) is presented for the determination of the CO 2 production (RCO 2 ) and energy expenditure in humans. This method is based on the simultaneous administration of [1- 13 C]glycine and [ 15 N]glycine followed by the measurement of excretion kinetics of breath 13 CO 2 and urinary 15 N. The basic idea of the DLAAM is that the unknown 13 C recovery RF( 13 C) of the 1- 13 C amino acid, essential for the calculation of the net CO 2 production, can be approximated by the easily measureable 15 N recovery RF( 15 N) of the α- 15 NH 2 labelled amino acid. In four healthy adult men (76-97 kg) the DLAAM was tested parallel to the IC and in one man (74 kg) parallel to the DLWM. Using the approximation RF( 13 C) ≈ RF( 15 N) the RCO 2 (in l CO 2 d -1 ) was calculated to 387.0 ± 30.3 (DLAAM) vs. 382.8 ± 22.6. (IC). The Bland-Altman plot shows that the difference between the DLAAM and IC of individual RCO 2 is within the 95 % confidence interval (mean ± 2 SD): +4.3 ± 37.5 l CO 2 d -1 . We conclude that the DLAAM and IC may be used interchangeably. The physical activity level (PAL) was calculated based on the DLAAM vs. DLWM to about 1.5.

Exhaled nitric oxide (F E NO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower F E NO values, and the clinical use of F E NO values in COPD patients is unclear. Therefore, we investigated if F E NO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD ( n  = 533, 58% females) were investigated while in stable condition. Measurements of F E NO 50 , blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers ( n  = 150) had lower F E NO 50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did ( n  = 383) 15 (14, 16) ppb, p  < 0.001. F E NO 50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found ( r  = 0.23, p  < 0.001) and ( r = -0.18, p  = 0.001), respectively. Lower F E NO values were associated with lower FEV 1 % predicted in both smokers ( r  = 0.17, p  = 0.040) and ex-smokers ( r  = 0.20, p  < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in F E NO 50 . Ex-smokers treated with inhaled corticosteroids (ICS) had lower F E NO 50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p  = 0.024. This was not found in smokers ( p  = 0.325). F E NO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of F E NO as an inflammatory marker is more limited in smoking subjects. The association found between low F E NO values and low lung function requires further investigation.

Background : Essential oils are volatile compounds of plant origin increasingly used by allergic and/or asthmatic subjects to purify indoor air. The active compounds of essential oils belong to terpenes, the most widespread biogenic volatile organic compounds (VOC). Although there is substantial literature showing associations between exposure to chemical VOCs and asthmatic symptoms and impaired respiratory function, the impact of essential oils in patients with asthma has never been studied. Objectives : To evaluate the safety of a purifying air spray containing 41 essential oils (PPAS) in patients with mild or moderate allergic asthma. Methods : This was a prospective open study in which 25 mild (19) and moderate (6) asthmatics were exposed to PPAS, one spray twice a day at 8 am and 8 pm in two different corners of a given subjects bedroom for 4 weeks. Before and after 4 weeks of exposure, fractional exhaled nitric oxide (FeNO), lung function and methacholine challenge (PD 20 ) were performed and asthma control was assessed by the 5 questions of the Asthma Control Test (ACT). The spray was weighed after the 4-week exposure to assess compliance. Results : FeNO was the primary endpoint and was thus analyzed in all ( N  = 25) subjects irrespective of the level of airflow obstruction. The results apply to all ( N  = 25) subjects in which FeNO could be measured at D1 and D30 (17 subjects). Mean (SD) FeNO amounted to 37.4 (16.6) and to 33.1 (18.7) ppm before and after PPAS exposure, respectively ( p  = 0.09). No significant change in lung function and methacholine responsiveness was noted after PPAS exposure, the mean PD 20 amounting to 1179 (1124.42) μg (range 100-3200) before and to 1226 (1189.8) μg ( p  = 0.06) after. The mean ACT before and after PPAS exposure amounted to 20.9 (4.2) and 21 (5.15), respectively ( p  = 0.80). The mean weight of the PPAS bottles was 211.4 g (DS:0) before the first use and 171.41 g (DS: 29.8) at the end of the study. The average amount of PPAS used was 40.0 g (29.8). In the subgroup of subjects who used the highest quantities of essential oils (>40 g), as assessed by the mean weight of the bottle at the end of the study, FeNO after 30 days of exposure decreased more than in the entire group: 7.9 ppm vs 4.2 ppm ( p  = 0.07). Conclusion : No difference was noted on airway inflammation, lung function or asthma control in mild and moderate allergic asthmatics after exposure twice a day for one month, to a spray containing a mixture of 41 essential oils.

Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity., Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks., Results: The proportions of patients with technically acceptable measurements at 10-30-50-100-150-200-250-300 mL/s exhalation flow rates were 8-58-100-98-98-95-90-80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100-150-200-250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83-2.97/vs. 0.70/0.54-0.87/nL/s, p < 0.001) and CANO (4.08/2.63-7.16/vs. 2.42/1.83-2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF 25-75% (p = 0.02, r = -0.36) and DL,CO (r = -0.46, p = 0.004). JawNO was not related to lung function parameters., Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100-250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma.

Biomarker measurements can provide unambiguous evidence of environmental exposures as well as the resultant biological responses. Firefighters have a high rate of occupational cancer incidence, which has been proposed to be linked in part to their increased environmental exposure to byproducts of combustion and contaminants produced during fire responses. In this article, the uptake and elimination of targeted volatile organic compounds were investigated by collecting the exhaled breath of firefighters on sorbent tubes before and after controlled structure burns and analyzing samples using automated thermal desorption-gas chromatography (ATD-GC/MS). Volatile organic compounds exposure was assessed by grouping the data according to firefighting job positions as well as visualizing the data at the level of the individual firefighter to determine which individuals had expected exposure responses. When data were assessed at the group level, benzene concentrations were found to be elevated post-exposure in both fire attack, victim search, and outside ventilation firefighting positions. However, the results of the data analysis at the individual level indicate that certain firefighters may be more susceptible to post-exposure volatile organic compounds increases than others, and this should be considered when assessing the effectiveness of firefighting protective gear. Although this work focuses on firefighting activity, the results can be translated to potential human health and ecological effects from building and forest fires.

Objective: The aim of this work was to compare matrix metalloproteinase-9 and -12, tissue inhibitor of metalloproteinase-1 and -4, and neutrophil elastase in exhaled breath condensate (EBC) and peripheral blood of patients with COPD. Methods: Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR. Results: The protein levels of MMP-9 ( p =.034) and MMP-12 ( p =.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 ( p =.072) and TIMP-4 ( p =.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 ( r =-0.78, p <.0001) and TIMP-1 ( r =-0.71, p <.0001) levels in EBC were significantly negatively correlated with pulmonary function FEV 1 %pred. The protein levels of MMP-12 ( r =-0.37, p =.034) and TIMP-4 ( r =-0.34, p =.041) were also negatively correlated with FEV1%pred. The expression of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in PBMCs and serum of COPD smokers were significantly higher than those of control never-smokers ( p <.05). Conclusions: Exhaled MMP-9, MMP-12, TIMP-1, and TIMP-4 levels increased in stable COPD patients and were negatively correlated with FEV1%pred, which suggests the usefulness of their measurement in EBC for the monitoring of airway inflammation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.

Carbon isotopes of breath CO 2 vary depending on diet and fuel substrate used. This study examined if exercise-induced δ 13 C-CO 2 changes in substrate utilization were distinguishable from baseline δ 13 C-CO 2 variations in a population with uncontrolled diet, and compared hair isotope values and food logs to develop an isotope model of diet. Study participants included nine women with diverse Body Mass Index (BMI), age, ancestry, exercise history, and diet. Breath samples were collected prior to and up to 12 h after a 5- or 10 K walk/run. Indirect calorimetry was measured with a smartphone-enabled mobile colorimetric device, and a field-deployable isotope analyzer measured breath δ 13 C-CO 2 values. Diet was assessed by food logs and δ 13 C, δ 15 N of hair samples. Post-exercise δ 13 C-CO 2 values increased by 0.54 ± 1.09‰ (1 sd, n = 9), implying enhanced carbohydrate burning, while early morning δ 13 C-CO 2 values were lower than daily averages (p = 0.0043), indicating lipid burning during overnight fasting. Although diurnal δ 13 C-CO 2 variation (1.90 ± 0.77‰) and participant baseline range (3.06‰) exceeded exercise-induced variation, temporal patterns distinguished exercise from dietary isotope effects. Hair δ 13 C and δ 15 N values were consistent with a new dietary isotope model. Notwithstanding the small number of participants, this study introduces a novel combination of techniques to directly monitor energy balance in free-living individuals.

Objective: Rheumatoid arthritis (RA) is an autoinflammatory disease caused by genetic susceptibility and environmental triggers, which include infectious agents. Helicobacter pylori, a bacterium that frequently colonizes the stomach, is associated with the development of certain autoinflammatory disorders. This study examined a possible association between H. pylori infection and RA., Method: This cohort study was performed in the Central Denmark Region. Patients were enrolled from primary healthcare centres after a urea breath test (UBT) for H. pylori and followed for a median of 8 years. Nationwide administrative registries provided information about the patients' diagnoses, country of birth, and gender. Comorbidity was determined using the Charlson Comorbidity Index. We compared the prevalence of RA via odds ratios (ORs) and incidences using Cox regression to calculate the hazard ratios (HRs) by comparing H. pylori-positive and H. pylori-negative individuals and adjusting for confounding variables., Results: A total of 56 000 people diagnosed as H. pylori positive or negative had similar rates of comorbidity. No link was found between H. pylori and RA. There was no difference in RA prevalence until time of UBT [OR = 0.91, 95% confidence interval (CI) 0.70-1.19)] or incidence of new RA cases after UBT (HR = 0.80, 95% CI 0.56-1.13) between H. pylori-positive and -negative subjects. Validation via four other RA definitions provided similar results., Conclusion: This study found no association between H. pylori infection and RA. This result does not support the involvement of H. pylori in a gut-joint axis of importance for RA development.

Background: Investigations examining the association between pregaming, or the consumption of alcohol prior to attending a social gathering or drinking establishment, and blood alcohol concentrations have primarily relied on estimations (i.e., Widmark equation), rather than objective biologic samples, such as breath alcohol concentration (BrAC)., Objectives: The current study assessed: (1) pregaming, using quantity-based measures, among a sample of college and non-college affiliated bar patrons, (2) associations between pregaming intensity/status and participant intoxication (BrAC), and (3) whether participants who pregamed were more likely to identify as a hazardous drinker., Methods: 548 bar patrons provided data on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and a single pregaming item assessing quantity of alcohol consumed prior to visiting a bar/restaurant district in 2015. BrAC samples were collected post interview. We used hierarchical linear regression models, respectively, to assess whether pregaming significantly impacted BrAC and whether presence of hazardous drinking predicted pregaming behavior., Results: After controlling for sex, race/ethnicity, age, student status, and Greek affiliation, the linear regression model explained 32.3% (R 2  = .323) of the variance of BrAC levels (F(12) = 21.162, p < .001), with 4.30% of the variance explained solely by pregaming (β = 0.014; p < .001). The linear regression model to assess if harzardous drinking behavior (AUDIT-C) significantly predicted pregaming explained 31.2% (R 2  = .312) of the variance of pregaming behavior (F(18) = 13.276, p < .001), with 4.2% of the variance explained solely by AUDIT-C scores (β = 0.280; p < .001)., Conclusion: Findings further highlight pregaming as a harmful risk behavior linked to elevated levels of hazardous drinking and intoxication.

Background: Alcohol consumption and related consequences is a problem on many college campuses. Tailgating parties before college sporting events may be contributing, however, little recent research has investigated alcohol consumption at these events., Objective: The purpose of this study is to evaluate the drinking behaviors of college game day tailgate attendees and subsequent alcohol-related consequences., Methods: Participants (N = 89; 44.9% female) were recruited from tailgates at a university in the Midwest United States on college football game days during fall 2014. Participants provided a breath sample, completed a questionnaire, and were given the opportunity to participate in a follow-up survey (n = 62) to assess resulting alcohol-related consequences., Results: Over half of participants had BrACs greater than 0.000. However, one in three participants reported intentions to abstain from alcohol or to drink but not enough to get buzzed. Intoxication intentions were a significant and unique predictor of alcohol consumption and experience with alcohol-related consequences at follow-up. Conclusions/Importance: This study updates and extends the literature on alcohol-related consequences in the context of college football tailgates. The results suggest that consequences may be prevented through changes in intentions to become intoxicated.

Objective: This literature review aims to compare obese-asthmatic adults and children, and to characterize differences and similarities between the two subgroups from epidemiological, demographical, phenotypical, and physiological perspectives., Methods: Literature search was conducted using Pubmed database with "obesity," "asthma," "epidemiology," "cluster analysis," "demography," "mechanics," and ''FeNO'' as search terms., Methods: Articles investigating epidemiological, demographic, phenotypical variation, and mechanical aspects of breathing specifically in obese asthmatics were identified. The studies were then divided according to age: children (<18 years of age) and adults (>18 years of age)., Results: Increase in asthma incidence and prevalence is observed in both obese-asthmatic children and adults. Asthma prevalence is greater in adult females regardless of ethnic background, and in men of African American and Hispanic ethnicities. Degree of weight gain and early onset of menarche appears to directly affect asthma severity in adolescent girls and females. Airway hyperresponsiveness and fractional exhaled nitric oxide do not have any positive correlation with high BMI in obese-asthmatic children and adults. Obesity also alters lung mechanics in asthmatics, but the impact is different for children and adults likely due to differential effect of obesity on central and peripheral airway., Conclusion: Existing literature suggests both similarities and differences in obese-asthmatic children and adults. The most pertinent differences are related to gender, ethnicity, and lung functions.

Introduction: Exhaled nitric oxide is believed be a useful surrogate for airways inflammation while non-adherence with therapy is known to be associated with worsening of asthma control., Case: We present the case of a 49-year-old female with steroid-dependent asthma and an exacerbation rate of >20/year. She was enrolled in a 3-month-long prospective study using a validated diagnostic inhaler device that provided objective evidence of inhaler compliance. Fractional exhaled nitric oxide (FeNO), peak expiratory flow rates, asthma control questionnaires were measured throughout the study period. Peripheral eosinophil count was obtained prior to the study, during the study, and immediately afterwards., Results: Improvement in compliance at the end of the study led to significant improvements in lung function peak expiratory flow rate (PEFR), and objective scores of asthma. There was an observed improvement in PEFR after 4 weeks, with an associated decrease in FeNO from 92 to 9 ppb that plateaued over the remainder of the study. Her eosinophil count was 0.79 × 10 9 /litre prior to starting in the study, 0.37 × 10 9 /litre after 2 months, and 0.1 × 10 9 /litre at the end of the study., Conclusion: We believe that this is the first case study to objectively prove that improvements in compliance can lead to dramatic reductions in the overall inflammatory airway response and in particular that improvements in patient compliance are mirrored by marked reduction in FeNO levels. These changes occurred in tandem with an observed clinical improvement in our patient.

Objective: Menopausal asthma is considered a distinct asthma phenotype. Our aim was to identify potential specific features of asthma in postmenopausal women in a cohort of Polish females., Methods: Asthma severity and control, pulmonary function, exhaled nitric oxide (FE NO ), peripheral blood and induced sputum (IS) differential cell count were compared in three groups: women with premenopausal asthma (group 1), menopausal women with pre-existing asthma (group 2A) and menopausal women with asthma onset in the perimenopausal or menopausal period (group 2B)., Results: We enrolled 27 women to group 1, 13 to group 2A and 16 to group 2B. Asthma severity and control, blood eosinophil count and FE NO did not differ among the groups. Menopausal women had a higher incidence of irreversible airway obstruction (84.6% in group 2A and 56.2% in group 2B vs. 22.2% in group 1, p < 0.001 and p = 0.03, respectively). The proportion of patients with sputum eosinophilia was highest in menopausal women with pre-existing asthma, although the difference did not reach statistical significance (88.9% in group 2A vs. 66.7% in group 2B and 65.0% in group 1, respectively, p = 0.86)., Conclusions: Menopausal women with asthma are characterized by an increased incidence of irreversible airway obstruction regardless of disease duration. This may indicate that age may contribute to pulmonary function impairment in asthmatic women independently of their hormonal status at the time of asthma diagnosis. Our results failed to confirm the presence of specific asthma features which would allow to distinguish the phenotype of menopausal asthma.

Objective: Airway hyperresponsiveness (AHR) is a hallmark of asthma. Methacholine challenge test which is mostly used to confirm AHR is not routinely available. The aim of this study was to investigate the predictive values of fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and plethysmography for the assessment of AHR in children with well-controlled asthma., Methods: 60 children with controlled allergic asthma aged 6-18 years participated in the study. FeNO measurement, spirometry, IOS, and plethysmography were performed. Methacholine challenge test was done to assess AHR. PC20 and dose response slope (DRS) of methacholine was calculated., Results: Mild to severe AHR with PC20 < 4 mg/ml was confirmed in 31 (51.7%) patients. Baseline FeNO and total specific airway resistance (SRtot)%pred and residual volume (RV)%pred levels in plethysmography were significantly higher and FEV1%pred, FEV1/FVC%pred, MMEF%pred values were lower in the group with PC20 < 4 mg/ml. FeNO, SRtot%pred, and RV%pred levels were found to be positively correlated with DRS methacholine. The higher baseline FeNO, frequency dependence of resistance (R5-R20) in IOS and SRtot%pred in plethysmography were found to be significantly related to DRS methacholine in linear regression analysis (β: 1.35, p = 0.046, β: 4.58, p = 0.002, and β: 0.78, p = 0.035, respectively). The cut-off points for FeNO and SRtot% for differentiating asthmatic children with PC20 < 4 mg/ml from those with PC20 ≥ 4 mg/ml were 28 ppb (sensitivity: 67.7%, specificity: 72.4%, p < 0.001) and 294.9% (sensitivity: 35.5%, specificity: 96.6%, p = 0.013), respectively., Conclusion: IOS and plethysmography may serve as reliable and practical tools for prediction of mild to severe methacholine induced AHR in otherwise "seemingly well-controlled'' asthma.

Superoxide dismutases (SODs) and catalase (CAT) have been implicated as major antioxidant enzymes of the human lungs. In this study, we investigated whether activities of these enzymes are altered in the airways of patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). SOD and CAT activities were measured in the sputum, exhaled breath condensate, and serum of 36 COPD patients experiencing a severe exacerbation. Measurements were performed using colorimetric assays in samples collected at the time of hospital admission and at the time of hospital discharge following treatment of AECOPD. For comparison, antioxidants were also assessed in 24 stable COPD patients and 23 healthy control subjects. SOD and CAT activities in sputum were significantly increased in patients with AECOPD compared to those with stable disease (SOD: 0.142 [0.053-0.81] vs. 0.038 [0.002-0.146] U/mL, p < 0.01; CAT: 48.7 [18.7-72.6] vs. 10.2 [2.9-40.6] nmol/min/mL, p < 0.05), while treatment of exacerbation led to a decrease in enzyme activities (SOD: 0.094 [0.046-0.45] U/mL, p < 0.05; CAT: 28.0 [7.3-60.4] nmol/min/mL, p < 0.005). No changes were observed in the serum (p > 0.05). Both SOD and CAT activities significantly correlated with sputum neutrophil and lymphocyte cell counts in patients with AECOPD. Moreover, SOD and CAT values correlated with each other and also with sputum malondialdehyde, an established marker for oxidative stress. Our data demonstrate that sputum antioxidant activity is elevated during COPD exacerbation and suggest that activation of SODs and CAT is an integral part of the human defense mechanism against the increased oxidant production associated with AECOPD.

Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N 2 -slope). The N 2 -slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV 1 ) to 25% among those with low FEV 1 , while increasing from 4% among those with the lowest N 2 -slope to 26% among those with the highest. However, combining the N 2 -slope and FEV 1 resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N 2 -slope and lowest FEV 1 , and less than 1% among never smokers with the lowest N 2 -slope and highest FEV 1 . Thus, combining the results of the single breath N 2 -slope and FEV 1 considerably improved the prediction of COPD events as compared to either test alone.

Chronic obstructive pulmonary disease (COPD) is the most common fixed airflow limitation. Individuals may present with the features of both asthma and COPD called asthma-COPD overlap (ACO) with more severity and worse health-related quality of life than COPD or asthma. One of the promising biomarkers that could be used in clinical practice to differentiate ACO from COPD is fractional exhaled nitric oxide (F ENO ). The role of Fractional exhaled nitric oxide (F ENO ) in COPD/ACO remains unknown. This scoping review aims to investigate the role of F ENO measurement to differentiate COPD from ACO, to anticipate disease severity/progression and treatment response. A structured comprehensive literature search was performed in major databases including Medline, EMBASE, CINAHL, Cochrane Library, Web of Science, and BIOSIS from 2005 onwards. Thirty-eight studies were retrieved. Based on the synthesis of the reviewed literature, six themes emerged. Thirty-four articles covered more than one theme. From which, 24 articles were on modifying factors in F ENO measurement, 18 on F ENO in COPD compared with healthy subjects, and seven on F ENO in ACO compared with COPD, 22 on F ENO and disease severity/progression,12 on F ENO and biomarkers, and eight on F ENO and treatment response. F ENO measurement cannot be used alone in the clinical settings of COPD patients. Although F ENO level is higher in ACO patients than COPD-only, it is still unclear if there is a F ENO cut-off that can be used to make the diagnosis of ACO and/or to guide therapy with inhaled corticosteroids/glucocorticoids in COPD patients.

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm 3 ) than the rest (CB: 23 ppb, 184 cells/mm 3 , emphysema: 27 ppb, 159 cells/mm 3 ; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.

Background: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare., Methods: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO 50 ), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated., Results: Asthma was associated with higher FeNO 50 levels irrespective of the UAD category. FeNO 50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO 50 levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund-Macay (ρ = -0.46, p = 0.03) and ACQ scores (ρ = -0.52, p = 0.009) in asthmatics with CRS., Conclusions: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO 50 levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

Background: Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups., Methods: This cohort (age 17-76 years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire., Results: Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01)., Conclusion: Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.

Background: Alcohol consumption and experiencing a concussion are positively correlated. Concussion history has not been examined previously in any alcohol field study (i.e., conducted in a natural setting)., Objective: To better understand the relationship between concussion history and alcohol consumption., Methods: We conducted two anonymous field studies among a 2015 sample of bar patrons (N = 544; 62.5% males) in a college town to assess concussion history and two alcohol consumption measures: (1) breath alcohol concentration (BrAC) levels and (2) hazardous drinking scores (based on the AUDIT-C). Next, we conducted a logistic regression analysis to predict concussion history using the two alcohol consumption measures and other potential covariates (i.e., age, gender, race, college student status)., Results: Among participants in our sample, the average BrAC level was.070 (SD =.053) and the average hazardous drinking score was 4.7 (SD = 2.5). Less than half of participants indicated that they had experienced a concussion in their lifetime (235; 43.2%). The logistic regression model indicated that hazardous drinking scores were significantly, positively associated with having experienced a concussion, whereas other covariates (i.e., BrAC, age, gender, race, college student status) did not significantly predict concussion history. Conclusions/Importance: Hazardous drinkers were more likely to have experienced a concussion. Therefore, the relationship found in this sample, between hazardous drinking behavior and concussion history, points to hazardous drinking as a possible risk factor for having had a concussion in the past.