Nitric Oxide In Exhaled Breath Research Articles

Waveguide-Based Microwave Nitric Oxide Sensor for COVID-19 Screening: Mass Transfer Modulation Effect on Hollow Confined WO3 Structures.

Serious acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a tremendous threat to global public health. Recently, the Food and Drug Administration approved the emergency use of volatile organic components as detection biomarkers for COVID-19, ushering in a new era of portable, simple, and rapid epidemiological screening based on breath diagnosis. Nitric oxide (NO) is an important biomarker indicating the degree of inflammation in the respiratory tract. In this study, a hollow multishelled structured WO3 (HoMSs-WO3)-based waveguide microwave gas sensor (MGS) was fabricated to detect trace levels of NO in exhaled breath for the preliminary diagnosis of COVID-19. The sensor showed excellent reusability and selectivity and efficiently detected NO in the 10-100 ppb, with a sensitivity of 39.27 dB/ppm and a detection limit of 2.52 ppb. In addition, a sound correlation was observed in the measurement results between the MGS and the Sunvou detector for detecting NO from the exhaled breath of clinical COVID-19 patients. The difference between the two measurements was within 1.96 standard bias, and the consistency range was -12 to 17 ppb, thus fully demonstrating the significant potential of the sensor in COVID-19 screening.

FMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

Does BMI Modify the Association between Vitamin D and Pulmonary Function in Children of the Mild Asthma Phenotype?

Vitamin D deficiency and obesity are global health problems that are associated with increased asthma risk in children. The purpose of this study was to investigate whether BMI modifies pulmonary function across vitamin D tertiles in pediatric asthma patients of the mild asthma phenotype. This cross-sectional study conducted from November 2016-September 2017 compared lung function variability as assessed by spirometry and nitric oxide in exhaled breath (FeNO) among 35 normal-weight and 26 overweight/obese Greek schoolchildren (5-12 years old) with mild asthma. Serum 25 (OH)D levels ≥ 30 ng/mL were defined as 'sufficient', 20-30 ng/mL 'insufficient', and <20 ng/mL 'deficient'. Stratification by BMI category, linear regression showed positive associations between D, % FVC (β = 0.49, 95%CI: 0.05, 0.94), and % FEV1 (β = 0.48, 95%CI: -0.01, 0.95) in the normal-weight only, adjusted for age, sex, regular exercise, and medication. FEV1 was 10% higher in the normal-weight D-sufficient group compared to those D-deficient (β = 10.43, 95%CI: 0.54, 20.32). No associations were observed for the overweight/obese group or FeNO. In conclusion, BMI modified associations of vitamin D on airway mechanics in children of the mild asthma phenotype. Serum 25 (OH)D concentrations ≥ 30 ng/mL were associated with higher ventilation in central airways of normal-weight asthmatic children.

Responsiveness of Inhaled Corticosteroid Treatment in Children with Asthma: The Role of rs242941 Polymorphism of CRHR1 Gene.

Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness. This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1s (FEV1) after treatment versus at inclusion. In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters. TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV1.

Measurement of nitric oxide spectral parameters: Considering the effects of CO2 and H2O

A continuous-wave quantum cascade laser (CW-QCL) based spectrometer is developed to investigate the high-resolution spectral parameters of nitric oxide (NO). Line strengths and nitrogen (N2)-, carbon dioxide (CO2)-, water vapor (H2O)-, broadening coefficients for NO R(6.5) are measured. The spectral region ranging from 1989 cm−1 to 1901 cm−1, which is suitable for the in situ laser sensing of trace NO, is investigated. Spectral parameters are determined by fitting absorption spectra with multi-peak Voigt profiles. The measured intensities are compared to the HITRAN2020 database to assess the performance of the system and a good agreement within ±5% is obtained for the established lines. The measurement results are useful for the design of a spectroscopic sensor for monitoring exhaled breath NO, vehicle exhaust, and industrial emissions.

Characteristics, phenotypes, mechanisms and management of severe asthma.

Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity

BackgroundViral infections, especially those caused by rhinovirus, are the most common cause of asthma exacerbations. Previous studies have argued that impaired innate antiviral immunity and, as a consequence, more severe infections contribute to these exacerbations. ObjectiveThese studies explored the innate immune response in the upper airway of volunteers with allergic rhinitis and asthma in comparison to healthy controls and interrogated how these differences corresponded to severity of infection. MethodsVolunteers with allergic rhinitis, those with asthma, and those who are healthy were inoculated with rhinovirus A16 and monitored for clinical symptoms. Tissue and nasal wash samples were evaluated for antiviral signature and viral load. ResultsBoth subjects with allergic rhinitis and asthma were found to have more severe cold symptoms. Subjects with asthma had worsened asthma control and increased bronchial hyperreactivity in the setting of higher fractional exhaled breath nitric oxide and blood eosinophils. These studies confirmed reduced expression of interferons and virus-specific pattern recognition receptors in both cohorts with atopy. Nevertheless, despite this defect in innate immunity, volunteers with allergic rhinitis/asthma had reduced rhinovirus concentrations in comparison to the controls. ConclusionThese results confirm that the presence of an allergic inflammatory disorder of the airway is associated with reduced innate immune responsive to rhinovirus infection. Despite this, these volunteers with allergy have reduced viral loads, arguing for the presence of a compensatory mechanism to clear the infection.Trial Registration: ClinicalTrials.gov Identifier: NCT02910401.

An Assessment of Various Phenotypes of Chronic Obstructive Pulmonary Disease

Context: Chronic obstructive pulmonary disease (COPD) is a multifactorial and heterogeneous disease. To approach this heterogeneity, an attempt to group patients with similar characteristics that could be associated with a differential clinical outcome has been done by using the term clinical phenotype. Aim: This study aimed to classify phenotypes of COPD, assess and compare demography, assess and compare functional status and comorbidities. Patients and Methods: A hundred stable COPD patients were studied to identify various phenotypes of COPD, clinical assessment (modified Medical Research Council grading), functional assessment (6-min walk test), spirometry (fraction of exhaled breath nitric oxide, diffusing capacity for carbon monoxide) and radiological assessment (high-resolution computerized tomography, echocardiography) and screening for obstructive sleep apnea by Berlin questionnaire. Chi-square test/Fisher's exact test was used for the analysis of qualitative data. Results: The mean age of subjects was 60.8 ± 9.2 years with male-to-female ratio 9:1. Out of total 100 COPD patients, 45% had emphysema phenotype, 15% had COPD with bronchiectasis, and 20% each had asthma COPD overlap and chronic bronchitis. COPD phenotype was most common in age group 56–65 years. Emphysema patients (48.6%) were underweight and obesity was found to be most common in chronic bronchitis (30%). Emphysema patients (91%) had maximum exacerbation during the past 1 year with mean 6-min walk distance (158.7 m) and mean forced expiratory volume in 1% was 37.5. Conclusion: This is the first study in India which provides comparative categorizations of the phenotypic subgroups of COPD on various parameters.

Single-Walled Carbon Nanotube-Based Biosensors for Detection of Bronchial Inflammation

Inflammation is a protective mechanism against invading pathogens and tissue damage. However, the inflammatory process is implicated in a wide range of diseases affecting all organs and body systems. Nitric oxide — a multifunctional signaling molecule that plays a critical role in systemic blood pressure homeostasis, prevention of platelet aggregation, antimicrobial resistance, immunoregulation, tumor suppression and as a neurotransmitter — is used as a surrogate marker for inflammation. However, the most commonly used Griess assay is an indirect and expensive method for the determination of nitric oxide concentration. Hence, single-walled carbon nanotube-based biosensors have been explored as real-time, sensitive, selective and safe methods to determine nitric oxide released during the inflammatory process. In this review, we explore current developments in single-walled carbon nanotube-based biosensors for the detection of nitric oxide in exhaled breath as a direct and noninvasive test for detection of bronchial inflammation.

Determination of nitric oxide using light-emitting diode-based colorimeter with tubular porous polypropylene membrane cuvette.

On the basis of the Griess-Saltzman (GS) reaction, an optical device for nitric oxide (NO) detection in exhaled breath and atmosphere was developed by employing the light-emitting diode (LED, 560nm) as the light source, light-to-voltage converter (LVC) as the detector, and porous polypropylene membrane tube (PPMT) as the cuvette. The PPMT was filled with GS reagents and covered with a coaxial jacket tube for gas collection and color reaction; two ends of the PPMT were connected with the LED and LVC to detect the change of light transmissivity in the wavelength range of 530 to 590nm mainly. A gas absorber filled with GS reagents was installed prior toanother absorber filled with KMnO4 solution to eliminate the interference of coexisting NO2. Under the optimized experimental conditions, the device achieved a limit of detection (3σ/k) of 4.4ppbv for NO detection. The linearity range of this device was divided into two segments, i.e., 25 to 100ppbv and 50 to 1000ppbv, with both coefficients of determination > 0.99. The relative standard deviation was 2.7% (n = 9, c = 100 ppbv), and the analytical time was 5.5min per detection. The minimum detectable quantity was decreased to 1.18ng, which was ~ 100 times lower than the original GS method (115ng). The present device was applied for determination of NO in exhaled breath, vehicle exhaust, and air. In addition to satisfactory spiking recoveries (i.e., 103% and 107%), the analytical results of the present device were in agreement with the results obtained by the standard method. These results assured the practicality of the developed device for NO detection in real environmental samples.

COPD exacerbation rates are higher in non-smoker patients in India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common among non-smokers exposed to solid fuel combustion at home. Different clinical characteristics in these patients may have significant therapeutic and prognostic implications.METHODS: We used medical record review and a questionnaire among COPD patients at 15 centres across India to capture data on demographic details, different types of exposures and clinical characteristics. Chest radiography and pulmonary function testing were performed in all 1984 cases; C-reactive protein and exhaled breath nitric oxide were measured wherever available.RESULTS: There were 1388 current or ex-smokers and 596 (30.0%) non-smokers who included 259 (43.5%) male and 337 (56.5%) female patients. Sputum production was significantly more common in smokers with COPD (P < 0.05). The frequency of acute symptomatic worsening, emergency visits and hospitalisation were significantly higher (P < 0.05) in non-smokers with COPD; however, intensive care unit admissions were similar in the two groups. There was no significant difference with respect to the use of bronchodilators, inhalational steroids or home nebulisation among smoker and non-smoker patients. The mean predicted forced expiratory volume in 1 sec in smokers (43.1%) was significantly lower than in non-smokers (46.5%).CONCLUSION: Non-smoker COPD, more commonly observed in women exposed to biomass fuels, was characterised by higher rate of exacerbations and higher healthcare resource utilisation.

The use of exhaled nitric oxide and peak expiratory flow to demonstrate improved breathability and antimicrobial properties of novel face mask made with sustainable filter paper and Folium Plectranthii amboinicii oil: additional option for mask shortage during COVID-19 pandemic.

BackgroundMedical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks.MethodsThis prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FENO) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth.ResultsSubjects assigned the LMC mask had a lowered FENO (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius.ConclusionsThe LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen.

Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica. A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO). Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis. CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

The relationship between serum vitamin D level and asthma.

OBJECTIVE:Several studies have established a relationship between low serum vitamin D levels and the onset of asthma in childhood. In this study, we aim to assess the relationship between vitamin D and asthma.METHODS:This study included 29 mild and 30 moderate persistent asthma and 38 healthy control group. Evaluation of the three groups was carried out in respect of serum vitamin D levels, Respiratory Function Test (RFT), and Exercise Provocation Test (EPT). The two asthma groups were also examined using the Asthma Control Test (ACT) and Nitric Oxide in Exhaled Breath (FeNO) level.RESULTS:The vitamin D levels of the mild and the moderate persistent asthma groups were determined to be lower than the vitamin D levels of the control group (p=0.007). A significant negative correlation was determined in all cases between the vitamin D levels and the broncho-reversibility percentage (p=0.0002). The negative correlation between the vitamin D levels and the broncho-reversibility percentage was more evident in the moderate persistent asthma group (p=0.0001). In the moderate persistent asthma group, a significant positive correlation was determined between the lowness of the maximum forced expiratory volume in EPT and a low vitamin D level (p=0.009). The ACT scores were lower, and the FeNO levels were higher in the moderate asthma group compared to the mild asthma group (p=0.0001).CONCLUSION:The findings showed that low serum vitamin D levels were observed more often in children with asthma, and there was a correlation with increased broncho-reversibility in the RFT and increased bronchial hyper-reactivity in the EPT.

Association of Childhood Adversity and Increased Inflammatory Reactivity to Traffic Air Pollution

Socially disadvantaged individuals are at greater risk for simultaneously being exposed to severe psychosocial stress in childhood as well as poor air quality across the life span. Recent evidence from different bodies of literature suggests that severe early life stress calibrates the immune system as to increase the inflammatory response to air pollution exposure. This synergistic effect between early life stress and air pollution could contribute to disparity in diseases such as cardiovascular disease, diabetes, depression, and certain types of cancer. In this study with healthy young adults, we examined the effect of early life stress on the inflammatory response to acute non-controlled exposure to traffic related air pollution. Participants answered the adverse childhood experiences (ACE) questionnaire prior to exposure, which consisted of watching a nature documentary on television for two hours while seating in a recreational vehicle (RV) parked within 30 ft. from an interstate highway. The air inside the RV had similar air pollutant levels as those immediately outside. Levels of nitric oxide in exhaled breath (eNO) as well as serum levels of interleukin-1&amp;#946; (IL-1&amp;#946;), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF&amp;#945;) were measured prior to, one hour after, and twenty-four hours after exposure. Change in inflammatory biomarker (eNO, IL-6, TNF&amp;#945;) levels induced by air pollution as a function of ACE score was examined with &amp;#8220;mixed&amp;#8221; effects linear regression. Significant positive associations between ACE scores and changes in eNO levels at one-hour post exposure, as well as with IL-1&amp;#946; and IL-6 levels twenty-four hours post exposure were observed. These results were strongly influenced by sex. These results support the hypothesis that early life stress might lead to an increased inflammatory reactivity to traffic related air pollution, which in turn could drive disparity of inflammation-related health problems.

Relationship between total serum immunoglobulin E levels, fractional exhaled breath nitric oxide levels and absolute blood eosinophil counts in atopic and non-atopic asthma: a controlled comparative study

Objective: Asthma is a prevalent non-communicable disease both in low- and high-income countries, including Nepal. Total serum immunoglobulin E levels and peripheral blood absolute eosinophil counts are known inflammatory markers of asthma. Fractional exhaled nitric oxide measurement in breath has also been proposed as a non-invasive biomarker to assess eosinophilic airway inflammation. This study explores the correlation between these three variables with the intent that one may replace the other in resource-limited setups. Approach: This prospective controlled trial evaluated 314 subjects with and without asthma, with the asthma group sub-divided into atopic and non-atopic categories. Total serum immunoglobulin E level, absolute eosinophil count in peripheral blood and fractional exhaled nitric oxide level were measured in all categories. Results: The geometric mean of immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 221.07 ± 774.55 IU/mL, 214 ± 360/uL and 37 ± 49 ppb in the asthma group and 59.13 ± 174.32 IU/mL, 164 ± 137/uL and 12 ± 21 ppb in the control group, respectively. Significantly higher levels were seen in the asthma group for total serum immunoglobulin E (p < 0.001), AEC (p = 0.002) and FENO (p < 0.001) levels. Total serum immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 436.79 ± 822.40 IU/mL, 269 ± 395/uL and 76 ± 52 ppb in atopic asthma group. Similarly, total serum immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 131.17 ± 692.96 IU/mL, 182 ± 328/uL and 23 ± 22.5 ppb in non-atopic asthma group. Significantly higher levels were seen in all three variables: tIgE (p < 0.001), AEC (p = 0.008) and FENO (p < 0.001). A moderate degree of positive correlation was identified between tIgE and FENO50 (Spearman’s rho = 0.461) and tIgE and AEC (Spearman’s rho = 0.315) with only small correlation between FENO50 and AEC (Spearman’s rho = 0.299). Significance: tIgE levels, FENO50 and AEC levels are higher in asthma, specifically in the atopic phenotype, as compared to normal. Total serum IgE levels have moderate correlation with FENO50 and AEC but FENO50 and AEC are weakly correlated.

Diagnosis and Management of Severe Asthma.

Severe therapy-resistant asthma has been defined as "asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy". Patients who usually present with 'difficult-to-treat asthma' should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

Exhaled nitric oxide as a potential marker for detecting non-ulcer dyspepsia and peptic ulcer disease

Nitric oxide (NO) plays a key role in the development of peptic ulcer disease (PUD). Conversely, the gastric pathogen Helicobacter pylori colonizes the human stomach and contributes to the development of non-ulcer dyspepsia (NUD) and PUD. However, the underlying relation between molecular NO in exhaled breath and H. pylori-associated NUD and PUD remains largely unknown. Here, we found that the excretion kinetics of NO profiles in exhaled breath are altered markedly in H. pylori-infected NUD and PUD subjects. In our observations, PUD led to considerably higher enrichments of NO in exhaled breath compared to NUD, thus revealing a potential link between exhaled NO and ulcer and non-ulcer complications. Our findings therefore suggest that molecular NO in exhaled breath could be used as a potential biomarker for non-invasive diagnosis and selective differentiation of NUD from PUD. Our observations also highlight that alterations of NO in the gastric environment can play an important role in the pathogenesis of peptic ulcers and thus may provide a new strategy for precise evolution of the actual disease state without the need for endoscopic biopsy, even after the eradication of H. pylori infection.

Health impact of E-cigarettes: a prospective 3.5-year study of regular daily users who have never smoked

Although electronic cigarettes (ECs) are a much less harmful alternative to tobacco cigarettes, there is concern as to whether long-term ECs use may cause risks to human health. We report health outcomes (blood pressure, heart rate, body weight, lung function, respiratory symptoms, exhaled breath nitric oxide [eNO], exhaled carbon monoxide [eCO], and high-resolution computed tomography [HRCT] of the lungs) from a prospective 3.5-year observational study of a cohort of nine daily EC users (mean age 29.7 (±6.1) years) who have never smoked and a reference group of twelve never smokers. No significant changes could be detected over the observation period from baseline in the EC users or between EC users and control subjects in any of the health outcomes investigated. Moreover, no pathological findings could be identified on HRCT of the lungs and no respiratory symptoms were consistently reported in the EC user group. Although it cannot be excluded that some harm may occur at later stages, this study did not demonstrate any health concerns associated with long-term use of EC in relatively young users who did not also smoke tobacco.

Predictive Biomarkers for Asthma Therapy.

Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.