Exhaled Nitric Oxide Research Articles

Type-2 Inflammation in Health and Disease: Prevalence, Risk Factors and Multimorbidity

Background: In patients with airflow obstruction, the levels of biomarkers of Type-2 (T2) inflammation serve to predict the effectiveness of inhaled corticosteroid and biological therapies. Elevated biomarkers of T2 inflammation, including fractional exhaled nitric oxide (FeNO, ≥20 ppb) and blood eosinophil counts (BEC, ≥300 cells/µL), were investigated in a population-based cohort of the Austrian LEAD study. Methods: A total of 4976 individuals (aged 18–82 years) were categorised into four groups based on their FeNO and BEC levels: normal with FeNO < 20 ppb and BEC < 300 cells/µL (n = 2634); FeNO ≥ 20 ppb only (n = 1623); BEC ≥ 300 cells/µL only (n = 340); and FeNO ≥ 20 ppb and BEC ≥ 300 cells/µL (n = 379). Results: In age- and sex-adjusted regression models, individuals with elevated BEC only were most associated with chronic cough and sputum production (odds ratios [95% CI]: 1.22 [0.78, 1.84] and 1.37 [1.13, 2.62], respectively), whilst individuals with both elevated T2 biomarkers were most associated with wheezing, dyspnoea and asthma (odds ratios [95% CI]: 2.27 [1.56, 3.26], 1.32 [0.64, 2.50] and 3.63 [2.69, 4.88] respectively). Elevated levels of both FeNO and BEC presented an additive effect in extrapulmonary conditions, particularly in allergy, eczema and rhino conjunctivitis (odds ratios [95% CI]: 2.30 [1.84, 2.88], 1.37 [1.03, 1.81] and 2.95 [2.34, 3.70], respectively). Conclusions: T2 inflammation marked by elevated levels of FeNO and/or BEC is not only associated with respiratory conditions but also extends to extrapulmonary characteristics, with an additive effect.

Noninvasive, Multimodal Inflammatory Biomarker Discovery for Systemic Inflammation (NOVA Study): Protocol for a Cross-Sectional Study.

Prolonged systemic inflammation is recognized as a major contributor to the development of various chronic inflammatory diseases. Daily measurements of inflammatory biomarkers can significantly improve disease monitoring of systemic inflammation, thus contributing to reducing the burden on patients and the health care system. There exists, however, no scalable, cost-efficient, and noninvasive biomarker for remote assessment of systemic inflammation. To this end, we propose a novel, multimodal, and noninvasive approach for measuring inflammatory biomarkers. This study aimed to evaluate the relationship between the levels of inflammatory biomarkers in serum (gold standard) and those measured noninvasively in urine, sweat, saliva, exhaled breath, stool, and core body temperature in patients with systemic inflammation. This study is a single-center, cross-sectional study and includes a total of 20 participants (10 patients with systemic inflammation and 10 control patients). Eligible participants provide serum, urine, sweat, saliva, exhaled breath, and stool samples for biomarker analyses. Core body temperature is measured using a sensor. The primary end point is the level of C-reactive protein (CRP). The secondary end points are interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels. The tertiary end points are fractional exhaled nitric oxide, calprotectin, and core body temperature. Samples will be collected in 2 batches, enabling preliminary analysis of the first batch (patients 1-5 from each group). The full analysis will include both batches. CRP and cytokine levels will be measured using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. For statistical analysis, the Shapiro-Wilk test will be used to evaluate the normality of the distribution in each variable. We will perform the 2-tailed t test or Wilcoxon rank sum test to compare the levels of inflammatory biomarkers between patients with systemic inflammations and control patients. Pearson and Spearman correlation coefficients will assess the relationship between inflammatory biomarkers from noninvasive methods and serum biomarkers. Using all-subset regression analysis, we will determine the combination of noninvasive methods yielding the highest predictive accuracy for serum CRP levels. Participants' preferences for sampling methods will be assessed through a questionnaire. The study received ethics approval from the independent research ethics committee of Canton Zurich on October 28, 2022. A total of 20 participants participated in the study measurements. Data collection started on February 22, 2023, and was completed on September 22, 2023. Participants were on average 52.8 (SD 14.4; range 24-82) years of age, and 70% (14/20) of them were women. The analysis results reporting findings are expected to be published in 2025. This study aims to evaluate the feasibility of noninvasive, multimodal assessment of inflammatory biomarkers in patients with systemic inflammation. Promising results could lead to the creation of noninvasive and potentially digital biomarkers for systemic inflammation, enabling continuous monitoring and early diagnosis of inflammatory activity in a remote setting. DERR1-10.2196/62877.

Association between triglyceride-glucose index and fractional exhaled nitric oxide in adults with asthma from NHANES 2007–2012

BackgroundSeveral studies have shown a potential relationship between triglyceride-glucose index (TGI) and asthma. However, limited research has been conducted on the relationship between TGI and fractional exhaled nitric oxide (FeNO).MethodsA total of 1,910 asthmatic individuals from the National Health and Nutrition Examination Survey (NHANES) database were included in this study. Linear regression analyses were used to investigate the relationship between TGI and FeNO in patients with asthma. Subsequently, a trend test was applied to verify whether there was a linear relationship between the TGI and FeNO. Finally, a subgroup analysis was performed to confirm the relationship among the different subgroup populations.ResultsMultivariable linear regression analyses showed that TGI was linearly related to FeNO in the asthmatic population. The trend test additionally validated the positive linear relationship between TGI and FeNO. The result of XGBoost revealed the five most influential factors on FeNO in a ranking of contrasted importance: eosinophil (EOS), body mass index (BMI), poverty-to-income ratio (PIR), TGI, and white blood cell count (WBC).ConclusionsThis investigation revealed a positive linear relationship between TGI and FeNO in patients with asthma. This finding suggests a potential relationship between TGI and airway inflammation in patients with asthma, thereby facilitating the prompt identification of irregularities and providing a basis for clinical decision making. This study provides a novel perspective on asthma management.

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Evaluating serum periostin and YKL-40 as biomarkers for airway remodeling and hyperresponsiveness in pediatric asthma

BackgroundPeriostin and human chitinase-3-like protein 1 (YKL-40) have been suggested to be involved in the development of airway fibrosis and remodeling. This study aimed to investigate the relationship between serum periostin levels and airway hyperresponsiveness (AHR) and between serum YKL-40 levels and AHR in children with asthma, comparing periostin as a marker for Th2 inflammation and atopy with YKL-40. MethodsThe study involved children aged 6–15 years, comprising 75 with asthma and 29 healthy controls. We measured serum periostin and YKL-40 levels and performed exercise bronchial provocation tests, methacholine challenge tests, spirometry, and FeNO measurements. ResultsCompared to the healthy controls, asthmatic children exhibited significantly elevated levels of periostin (86.7 [71.0–104.0] vs 68.3 [56.0–82.0] ng/mL; P = 0.006) and YKL-40 (29.0 [15.0–39.5] vs 27.7 [14.0–34.1] ng/mL; P = 0.034). The subgroup analysis revealed that periostin levels were significantly higher in the atopic asthma group than in the healthy controls (P = 0.003), but not in the non-atopic asthma group. YKL-40 levels were elevated in both the atopic and non-atopic asthma groups compared to healthy controls (P = 0.012 and P = 0.001, respectively). Serum periostin levels were significantly correlated with the postexerceise maximum percentage decrease in forced expiratory volume (FEV1), as well as with fractional exhaled nitric oxide (FeNO) and blood eosinophil counts, but showed no significant correlation with overall lung function. Conversely, serum YKL-40 levels were significantly linked to the Z score of FEV1 and AHR to methacholine but not with AHR to exercise or FeNO or blood eosinophil count. ConclusionsPeriostin is linked to atopic asthma and correlates with exercise-induced bronchoconstriction, FeNO, and eosinophil counts, highlighting its role in Th2 inflammation. YKL-40 is a general asthma marker, indicating airway remodeling. These findings suggest that targeting these markers can improve personalized treatment strategies for pediatric asthma.

The anti-inflammatory role of therapeutic ultrasound and low-level laser in chronic rhinosinusitis: A fractional exhaled nitric oxide outcome hypothesis

Chronic rhinosinusitis is defined as a complex of disorders whose main feature is nasal and paranasal sinus mucosal inflammation for at least three months. Inflammation plays a key role in chronic rhinosinusitis. Fractional exhaled nitric oxide is used to monitor eosinophilic airway inflammation in the human lower airways. Fractional exhaled nitric oxide levels are paradoxically low in some chronic rhinosinusitis patients. This has been attributed to sinus ostia obstruction. However, a recent study has demonstrated that fractional exhaled nitric oxide levels could serve as a chronic rhinosinusitis inflammation biomarker independent of lower airway inflammatory disease and could be used as a treatment response biomarker. Therapeutic ultrasound and low-level laser therapy have been used in chronic rhinosinusitis management. Through a variety of mechanisms, ultrasound enhances bacterial killing. Low level laser therapy increases nitric oxide release and ATP levels. It also reduces inflammation and accelerates tissue repair. Fractional exhaled nitric oxide levels could be used to evaluate the anti-inflammatory actions of therapeutic ultrasound and low-level laser therapy in chronic rhinosinusitis patients. A hypothesis that fractional expired nitric oxide measurements could be a useful biomarker to evaluate their potential anti-inflammatory mechanisms and monitor their treatment efficacy is proposed. This could contribute to a better understanding of these therapies in chronic rhinosinusitis management. An improved understanding of treatment efficacy could lead to improved management strategies.

Clinical remission in patients with biologic-naïve asthma: a multicenter study in Japan

BackgroundClinical remission (CR) is a new realistic management goal for patients with asthma, regardless of the disease severity. ObjectiveTo investigate the rate of achievement of CR in patients treated with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) and non-biologics, and the characteristics of patients who achieved CR. MethodsWe performed a post hoc analysis from a multicenter, cross-sectional survey in Japan. 3-way CR was defined as the absence of exacerbation, no use of maintenance oral corticosteroids, and the absence of significant asthma symptoms (5-item Asthma Control Questionnaire [ACQ] < 1.5). We defined 4-way CR as 3-way CR plus having normalized lung function (forced expiratory volume [%FEV1] ≥ 80%). Deep remission (DR) was defined as 4-way CR plus suppressed type-2 airway inflammation (fractional exhaled nitric oxide [FeNO] < 35 ppb). ResultsThe criteria for 3-way CR, 4-way CR, and DR were met by 56.9%, 35.0%, and 24.7% of patients, respectively. Compared to patients who achieved the 3-way CR, unachieved patients have lower %FEV1 (77.6% vs. 85.4%, p<0.0001), higher FeNO levels (42 ppb vs. 34 ppb, p=0.0182), and there were more discordances in asthma control perception between patient-physicians (38.5% vs. 9.3%, p<0.0001). Physician-patient discordance was an independent factor that prevented the achievement of the 3-way CR in the logistic regression analysis, even when adjusted for %FEV1 and FeNO (odds ratio 0.397, p<0.0001). ConclusionAchieving CR in patients treated with ICS/LABA without biologics is challenging. Discrepancies between patient and physician perceptions on asthma control are significant barriers to achieving CR.

A protocol for a Japanese prospective cohort evaluating the features of patients with uncontrolled asthma achieving clinical remission: J-CIRCLE

BackgroundIncreasing expectations that biologics can be used as disease-modifying agents have introduced the concept of clinical remission (CR) in managements of severe asthma. Given the clinical relevance of computed tomography (CT) and blood biomarkers, we hypothesized that further refinement of CR criteria as well as incorporation of CT and blood biomarkers as indicators for structural and biological remission (SR, BR) would enable predicting long-term disease stability in patients with severe asthma treated with biologics. MethodsThis Japanese multicenter prospective observational cohort will enroll patients with severe asthma who will start a new biologic (including a change from another biologic). The enrolled patients will be longitudinally followed up for 3 years. At enrollment, patients will undergo postbronchodilator spirometry, blood tests, fractional exhaled nitric oxide, chest and sinus CT, and patient-reported outcome questionnaires. Follow-up examinations will be performed at 1, 3, 6, 12, 24, and 36 months. The rates of CR resulting from different criteria after 1 year of treatment with biologics will be compared, and factors associated with long-term disease stability after 3 years of biologic treatments will be identified. DiscussionThis multicenter study in Japan will provide data that will help establish more appropriate criteria for CR, structural remission, and biological remission to predict long-term disease stability in patients with severe asthma who receive biologic therapy. Ethics and disseminationThe study was approved by the Ethics Committee of Kyoto University (No. R4419, approval date June 11th, 2024). Trial registrationThe University Hospital Medical Information Network (UMIN000053771).

Modeling severe uncontrolled asthma: transitioning away from health states

BackgroundModels developed to date to simulate long-term outcomes of asthma have been criticized for lacking granularity and ignoring disease heterogeneity. ObjectiveTo propose an alternative approach to modeling asthma and apply it to model long-term outcomes in a population with moderate-to-severe type 2 asthma (patients with raised fractional exhaled nitric oxide or eosinophils) and treated with conventional therapy. MethodsA discretely integrated condition event (DICE) approach was adopted, simulating individual profiles with asthma over patients’ lifetime in terms of exacerbations, asthma-related death, and death unrelated to asthma. The timing of these events is dependent on profile characteristics including lung function, asthma control, exacerbation history, and other baseline characteristics or contextual factors. Predictive equations were derived from a clinical trial to model time to exacerbation, change in asthma control, lung function, and utility. Real-world studies were used to supplement data gaps. Outcomes evaluated included life expectancy, quality-adjusted life-years (QALY), number of exacerbations, and lung function over time. ResultsAverage annual rates of severe and moderate exacerbations were 1.82 and 3.08 respectively, with rates increasing over time. Lung function declined at a higher rate compared with the general population. Average life expectancy was 75.2 years, compared with 82.4 years in a matched general population. The majority of life-years were spent with uncontrolled asthma and impaired lung function. ConclusionPatients with moderate-to-severe type 2 asthma and a history of exacerbations suffer from frequent exacerbations and reduced lung function and life expectancy. Capturing multiple conditions to simulate long-term outcomes in patients with asthma may provide more realistic projections of exacerbation rates.

One-ElectronNO to N2O Pathways via Heme Models and Lewis Acid: Metal Effectsand Differences from the Enzymatic Reaction.

Some pathogens use heme-containing nitric oxide reductases (NORs) to reduce NO to N2O as their defense mechanism to detoxify NO and reduce nitrosative stress. This reduction is also significant in the global N cycle. Our previous experimental work showed that Fe and Co porphyrin NO complexes can couple with external NO to form N2O when activated by the Lewis acid BF3. A key difference from conventional two-electron enzymatic reaction is that one electron is sufficient. However, a complete understanding of the entire reaction pathways and the more favorable reactivity for Fe remains unknown. Here, we present a quantum chemical study to provide such information. Our results confirmed Fe's higher experimental reactivity, showing advantages in all steps of the reaction pathway: easier metal oxidation for NO reduction and N-O cleavage as well as a larger size to expedite the N/O coordination mode transition. The Co system, with a similar product energy as the enzyme, shows potential for further development in catalytic NO coupling. This work also offers the first evidence that this new one-electron NO reduction is both kinetically competitive and thermodynamically more favorable than the native pathway, supporting future initiatives in optimizing NO reduction agents in biology, environment, and industry.

Long-Term Exposure to Nitrogen Dioxide and Ozone and Respiratory Health in Children.

Further evaluation of the impact of long-term exposure to the gaseous air pollutants nitrogen dioxide (NO2) and ozone (O3) on child lung function, and of NO2 or O3 on eosinophilic airway inflammation, is needed. To determine whether NO2 and O3 are associated with lung function and FeNO in children. We measured lung function (FEV1 and FVC) at mid-childhood (mean age 7.9 years, n=703), early teens (13.2 years, n=976), and mid-teen (17.6 years, n=624) study visits, and fractional exhaled nitric oxide (FeNO) at the early and mid-teen study visits in Project Viva, a cohort of mother-child pairs in the Boston, MA area. Long-term exposure to NO2 and O3 was estimated at home address using geospatial models. We examined associations of home address NO2 and O3 exposure and proximity to roadway with lung function and FeNO using linear regression models, adjusting for age, sex, height, weight, season, relative humidity, temperature, parental smoking, and measures of socioeconomic status. We examined for effect modification of the mid-teen associations by blood eosinophil level, physical activity, aeroallergen sensitization, and parental atopy. Median exposure to NO2 was 33.1 ppb (interquartile range [IQR] 10.4 ppb) and to O3 was 35.3 ppb (IQR 3.4) in the first year of life. Exposure to NO2 was associated with lower FEV1 and FVC across all age groups and exposure time intervals: e.g. an IQR increment of NO2 exposure from birth through the early teen visit was associated with 189.9 mL lower FEV1 (95% CI -273.3, -106.5) at the mid-teen visit. Lifetime NO2 exposure at was associated with higher FeNO at the early teen visit: e.g. 16.2% higher FeNO [95% CI 7.1-26.4%) per IQR of lifetime NO2 through the early teen visit. O3 exposure was not associated with lung function or FeNO. Aeroallergen sensitization (measured in a subset of participants) modified associations of NO2 and O3 with FeNO. Exposure to NO2 was associated with lower lung function and higher FeNO among generally healthy children and teenagers. As NO2 exposure levels were within the annual EPA standard, these findings suggest a need to reduce exposure to this pollutant to optimize child respiratory health.

Effectiveness of paediatric asthma hubs: a clinical pilot study

BackgroundChildren and young people (CYP) with asthma in the UK are at higher risk of poor outcomes compared with other high-income European countries due to factors including poor access to high-quality asthma reviews, diagnostic testing and inconsistent postattack reviews. The Leicester Integrated Care Board funded the first UK pilot asthma hub for CYP, to investigate the feasibility and effectiveness of hubs, in providing postattack reviews along with providing asthma education, the opportunity to carry out diagnostic lung function tests and optimise treatment.MethodsClinical pilot study including CYP aged 4–17 years referred to the hub with uncontrolled asthma or postattack from November 2021 to April 2022. CYP received a structured clinical assessment including National Institute for Health and Care Excellence (NICE) first-line diagnostic investigations for asthma including spirometry, bronchodilator reversibility (BDR) and fraction of exhaled nitric oxide (FeNO).ResultsOf 312 CYP referred (mean age 8.6±3.2 years; 42% women), 266 (85.3%) attended their appointment. Median time from referral to review was 2 days (IQR 1–3). Three CYP (1.1%) were severely unwell at review and required further hospital treatment. In the 231 CYP who completed first-line tests, asthma was confirmed for 73 (31.6%) based on NICE diagnostic criteria for CYP. Twenty-two per cent of children with normal baseline spirometry had ≥12% BDR.ConclusionPaediatric asthma hubs are a feasible model of care to deliver CYP postasthma attack reviews and identify high-risk patients requiring further treatment. Spirometry, BDR and FeNO testing allowed diagnostic confirmation in a significant proportion of CYP.

Examining the effect of salbutamol use in ozone air pollution by people with exercise-induced bronchoconstriction.

Previous studies based on animal models have raised concerns about salbutamol use in ozone air pollution with regard to ozone related lung injury. We conducted a double-blind, randomized, placebo-controlled crossover study including 18 subjects diagnosed with EIB by a eucapnic voluntary hyperpnea (EVH) test. Participants completed 30 min of standardized moderate to vigorous exercise in four conditions: ozone plus salbutamol; room air plus salbutamol; ozone plus placebo medication; and room air plus placebo medication. Spirometry, fraction of exhaled nitric oxide, and symptoms were measured before, immediately after, 30 min after and 1 h after exercise. Measurements between the four conditions were compared using percent change from pre to post exercise. There was a statistically significant difference between the salbutamol and placebo medication groups for spirometric variables including FEV1 (Estimate = 6.3, 95% CI: 4.23-8.37, p < 0.001). No differences were observed between ozone and room air exposures. There were no significant differences in FeNO response between experimental conditions. We found that salbutamol improved pulmonary function in individuals with EIB when exercising in ozone and did not increase eosinophilic airway inflammation as indicated by FeNO. This evidence suggests that it is safe for people with EIB to continue to use salbutamol as proscribed when ozone levels are elevated.

Features of Idiopathic Halitosis and Its Association With Low-Grade Systemic Inflammation.

Idiopathic halitosis is occasionally encountered in clinical practice, yet with scarce reports. This work aimed to investigate its features and potential association with low-grade systemic inflammation (LGSI). This retrospective study reviewed idiopathic halitosis from 2469 halitosis patients and compared them with 63 healthy controls (HCs). Organoleptic score (OLS), exhaled volatile sulfur compounds (VSCs), serum inflammatory cytokines, and fractional exhaled nitric oxide (FeNO200) to indicate LGSI were determined. Totally, 54 (2.19%) idiopathic halitosis patients were identified and they were extraoral. Dimethyl sulfide (DMS) was found to be the primary exhaled VSC. Inflammatory cytokines were slightly elevated in 5.56% (3/54) of idiopathic halitosis compared to none of HCs (p = 0.095). FeNO200 was elevated in 79.63% (43/54) of idiopathic halitosis compared to none of HCs (p < 0.001), with a sensitivity of 79.63% and specificity of 100% for the diagnosis of idiopathic halitosis. The FeNO200 level had positive correlations with OLS (r = 0.871) and DMS level (r = 0.485). Idiopathic halitosis is a rare condition which is closely associated with LGSI and possibly caused by unexplored extraoral pathologies. FeNO200 is recommended for its diagnosis with a high diagnostic power.

Individual Inhalation Exposure to Phthalates and Their Associations with Anthropometric and Physiological Indices in Primary School Children in Jinan, China

Phthalates are commonly found in indoor environments. Consequently, children may be exposed to phthalates through the air, potentially causing health issues. We collected 72 air samples from 60 households and 12 classrooms in Jinan, surveyed and health-examined children, assessed their phthalate inhalation exposure, and analyzed the associations between inhalation exposure levels and children’s anthropometric and physiological indicators. Eight phthalates were detected in children’s households and classrooms, with detection frequencies ranging from 91.6% to 100%. Di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di (2-ethylhexyl) phthalate (DEHP) were the predominant phthalates. Children’s indoor inhalation exposure to phthalates ranged from 8.90 to 147 ng/(kg·day), with DEHP being the main inhaled phthalate. The non-carcinogenic risks of indoor environments where children live are within acceptable limits. DEHP has a low carcinogenic risk. Di-n-octyl phthalate (DnOP) exposure was associated with a decrease in body mass index z-score, waist circumference, and hip circumference. Additionally, DEHP exposure was negatively associated with the waist-to-hip ratio. DiBP exposure was negatively associated with the systolic blood pressure z-score, while DnOP exposure was negatively associated with the diastolic blood pressure z-score. Furthermore, DEHP exposure was positively associated with fractional exhaled nitric oxide z-score. The findings of this study suggest that phthalate inhalation exposure may substantially affect various health metrics in children, including body mass index, waist and hip circumference, and blood pressure, and increase the risk of respiratory tract inflammation.

Stability of severe asthma phenotypes

Introduction. Severe asthma (SA) is a heterogeneous disease with several phenotypes. There are lack of data about its stability.Aim. To assess stability of SA phenotypes in adult patients during 5 years follow-up.Materials and methods. Prospective study included 117 adult outpatients with allergic SA, 51 severe asthmatics with aspirin-induced disease, 59 patient with persistent airflow limitation (PAL) and 35 patients with SA and concomitant COPD, 65 steroid-dependent severe asthmatics and 89 patients with SA and frequent (≥2 per year) exacerbations. Spirometry and bronchodilator reversibility testing were carried out; fractional exhaled nitric oxide (FeNO) was measured; hypersensitivity to common inhalant allergens (skin prick and blood specific IgE testing) and peripheral blood eosinophil counts were estimated. Asthma control and asthma-related quality of life were assessed by using ACQ-5 and SGRQ questionnaire.Results. During 5-year prospective study stability of aspirin-induced SA and SA with COPD was 100%. Allergic phenotype was stable in 81% of SA cases and in patients with changed atopic status we revealed worsening of symptoms and accelerated lung function decline. Stability of SA phenotype with PAL without COPD was 86% and steroid-dependent SA was stable in 55% of cases. After 5 years of treatment frequent exacerbations remained in 28% of severe asthmatics.Conclusion. The most stable phenotypes of SA were aspirin-induced and asthma with concomitant COPD. Less stable were allergic SA, steroid-dependent SA and phenotype with persistent airflow limitation. The least stable was SA phenotype with frequent exacerbations.

Severe asthma phenotypes and endotypes

Introduction. Severe asthma is a heterogeneous disease with several phenotypes and endotypes. However, little is known about frequency of severe asthma phenotypes and endotypes in Russia.Aim. To assess frequency of severe asthma phenotypes and endotypes compared with mild/moderate asthma.Materials and methods. Cross-sectional single center study included 643 adult outpatients with mild/moderate asthma and 314 patients with severe asthma (SA) aged 18–90 years. Spirometry and bronchodilator reversibility testing were carried out. Fractional exhaled nitric oxide (FeNO) was measured by a chemiluminescent analyzer (logan 4100, UK). Hypersensitivity to common inhalant allergen was assessed by skin prick and blood specific IgE level. Peripheral blood eosinophil counts were measured by automatic analyzer. Asthma control and asthma-related quality of life were assessed by using ACQ-5 and SGRQ.Results. Allergic phenotype was more frequent in patients with mild/moderate asthma than in those with SA, but aspirin-induced asthma, steroid-dependent asthma, asthma with persistent airflow limitation and concomitant COPD, asthma with late onset and obesity were more frequent in SA. The majority of patients with SA had several phenotypes (mean 3 phenotypes) and at least one marker of T2-high endotype.Conclusion. The most frequent phenotypes of SA were allergic, with persistent airflow limitation, with concomitant obesity and COPD. Occurrence of asthma phenotypes differed between patients with SA and mild/moderate asthma. The majority of SA patients have T2-endotype.

Temporal trends and practice variation of paediatric diagnostic tests in primary care: retrospective analysis of 14 million tests

ObjectiveThe primary objective was to investigate temporal trends and between-practice variability of paediatric test use in primary care.Methods and analysisThis was a descriptive study of population-based data from Clinical Practice...

Nonasthmatic Eosinophilic Bronchitis: A Systematic Review of Current Treatment Options.

Nonasthmatic eosinophilic bronchitis is characterized by persistent dry or barely productive cough and bronchial eosinophilia without airway obstruction or bronchial hyperreactivity. It is primarily a chronic disease, in which some patients have clinical and pathophysiological relapses, while others progress to asthma or chronic obstructive pulmonary disease. It accounts for 5% to 30% of cases referred for chronic cough. Exposure to common inhalants and occupational sensitizers has been proposed as a possible cause of the disease, although the etiology and underlying mechanisms are uncertain. Some features are similar to those of asthma, such as airway eosinophilia, inflammatory mediator levels, and airway remodeling. Differences in airway pathophysiology, such as the location of airway inflammation and levels of IL-13 and PGE-2, have been reported. Sputum cell count is the gold standard test for diagnosis, and other biomarkers, such as exhaled nitric oxide, could support the diagnosis. A systematic review of treatments for the disease shows that while inhaled corticosteroids are the primary option, the appropriate dose, the type of corticosteroid, and the duration of treatment remain unknown. Treatment duration is inversely correlated with the relapse rate. Increased doses of inhaled corticosteroids, oral corticosteroids, and leukotriene receptor antagonists are recommended in persistent disease. Anti-IL-5 biologics could be promising in this disease. Studies that investigate biomarkers for diagnosis and prognosis are necessary, as are randomized controlled studies for second-line treatments.

Association between acute tobacco exposure and fractional exhaled nitric oxide in patients with chronic obstructive pulmonary disease: National health and Nutrition Examination Survey (NHANES) 2007–2012

BackgroundFractional exhaled nitric oxide (FeNO) is a marker of type 2 airway inflammation. Tobacco exposure can lower FeNO levels. However, the effect of acute tobacco exposure on FeNO in patients with chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate the relationship of acute tobacco exposure with FeNO and eosinophils in COPD patients. MethodsThis retrospective cohort study included 445 patients with COPD based on the 2007–2012 National Health and Nutrition Examination Survey. Serum cotinine levels were examined to assess environmental tobacco smoke exposure. The patients were divided into five groups based on cotinine levels: Q1 (first quintile), Q2 (second quintile), Q3 (third quintile), Q4 (fourth quintile) and Q5 (fifth quintile). Logistic regression models and linear logistic regression models were used to evaluate the relationship between serum cotinine and FeNO and EOS levels. ResultsApproximately 16.5 % (75/445) of the participants had elevated FeNO (>25 bbp). In the unadjusted model, COPD patients with the lowest quintile of serum cotinine levels (0.011–0.0185 ng/mL) had higher FeNO levels compared to those with the highest quintile (≥309 ng/mL) (odds ratios (OR), 5.86 [2.11–16.20]). These findings remained consistent even after adjusting for covariates of demographics, lifestyle, diabetes, coronary heart disease, tumours, hypertension, using oral or inhaled steroids within 2 days, asthma and respiratory symptoms within 7 days. Furthermore, a standard deviation increase of ln-transformed cotinine levels was associated with decreased FeNO levels (OR, 0.45 [0.33, 0.60]). No significant correlation was observed betweenserum cotinine and blood eosinophils. After high extents of tobacco exposure, no correlation was found between FeNO and eosinophils.Our findings indicate that high cotinine levels are associated with decreased FeNO in COPD patients but not with blood eosinophils. This reveals that smoking may affect FeNO levels in patients with COPD, whereas it does not appear to influence blood eosinophil levels.