Elevated Fractional Exhaled Nitric Oxide Research Articles

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Lack of association between Inhaled Corticosteroid use based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. We retrospectively analyzed 107 COPD patients without history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion [ppb] were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. The median FeNO value was 32 (Interquartile range [IQR], 19-45) ppb, and 34 (20.0%) patients were classified as high FeNO group (median 74ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥ 300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01-6.91; p = 0.049). High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation

BackgroundWhile a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (− 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (− 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation.MethodsOur study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (− 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method.ResultsIn our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 − 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001).ConclusionThis study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (− 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population

LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials. To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations. Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n= 832; or 37.5 mg, n= 829) or placebo (n= 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/μL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events. Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction: 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction:125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/μL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.

Association of Sputum Eosinophilia With Easily Measured Type-2 Inflammatory Biomarkers in Untreated Mild Persistent Asthma

A multicenter clinical trial in patients with mild persistent asthma indicated that response to inhaled corticosteroids (ICS) is limited to those with sputum eosinophilia. However, testing for sputum eosinophilia is impractical in most clinical settings. We examined associations between sputum eosinophilia and type 2 inflammatory biomarkers in untreated mild persistent asthma. Induced sputum, blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and serum periostin were obtained twice during the 6-week run-in period in a clinical trial that enrolled patients 12 years and older with symptomatic, mild persistent asthma without controller therapy. The optimal threshold for each biomarker was based on achieving 80% or greater sensitivity. Performance of biomarkers (area under the receiver operating characteristics curve [AUC], range 0.0-1.0) in predicting sputum eosinophilia 2% or greater was determined; AUCs of 0.8 to 0.9 and more than 0.9 define excellent and outstanding discrimination, respectively. Of 564 participants, 27% were sputum eosinophilic, 83% were atopic, 70% had BEC of 200/uL or higher or FeNO of 25 ppb or greater; 64% of participants without sputum eosinophilia had elevated BEC or FeNO. The AUCs for BEC, FeNO, and both together in predicting sputum eosinophilia were all below the threshold for excellent discrimination (AUC 0.75, 0.78, and 0.79, respectively). Periostin (in adults) had poor discrimination (AUC 0.59; P= .02). In untreated mild persistent asthma, there is substantial discordance between sputum eosinophilia, BEC, and FeNO. Until prospective trials test the ability of alternative biomarkers to predict ICS response, BEC or FeNO phenotyping may be an option to consider ICS through a shared decision-making process with consideration of other clinical features.

A cross-sectional analysis of medical conditions and environmental factors associated with fractional exhaled nitric oxide (FeNO) in women and children from the ISA birth cohort, Costa Rica

BackgroundFractional exhaled nitric oxide (FeNO) is a marker of airway inflammation. Elevated FeNO has been associated with environmental exposures, however, studies from tropical countries are limited. Using data from the Infants' Environmental Health Study (ISA) birth cohort, we evaluated medical conditions and environmental exposures’ association with elevated FeNO. MethodsWe performed a cross-sectional analysis of 277 women and 293 8-year old children who participated in the 8-year post-partum visit in 2019. We measured FeNO and collected information on medical conditions and environmental exposures including smoke from waste burning, work in banana plantations, and home pesticide use. We defined elevated FeNO as >25 ppb for women and >20 ppb for children. To evaluate factors associated with elevated FeNO, we used logistic regression models adjusted for obesity in women and unadjusted in children. ResultsOverall elevated FeNO was common (20% of women, 13% of children). Rhinitis diagnosis was significantly associated with elevated FeNO in both women (odds ratio (OR): 3.67 95% Confidence Interval (CI): 1.81,7.35) and children (OR: 8.18 95%CI: 3.15, 21.22); wheeze was associated with elevated FeNO in women (OR: 4.50 95% CI: 2.25, 8.99). Environmental exposures were associated with elevated FeNO, but not significantly. Waste burning was associated with elevated FeNO in both women (OR: 1.58 95%CI 0.68, 4.15) and children (OR: 2.49 95%CI:0.82, 10.79). Para-occupational pesticide exposures were associated with elevated FeNO in women and children. For women, having a partner working in agriculture was associated with elevated FeNO (OR: 1.61 95%CI:0.77, 3.58) and for children, maternal work in agriculture was associated with elevated FeNO. (OR 2.08 95%CI 0.86, 4.67) ConclusionRhinitis and wheeze were associated with elevated FeNO in this rural, agricultural population. Smoke from waste burning as well as para-occupational pesticide exposure may contribute to elevated FeNO in rural communities.

The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma

Asthma affects the respiratory system and causes airway inflammation. The indication of asthma includes a triad of airway inflammation, hyperresponsiveness, and obstruction. Nitric Oxide (NO) is a gas that is exhaled and is a sign of airway inflammation. NO levels in the exhaled breath of patients with type 2 asthma are elevated, and fractional exhaled nitric oxide (FeNO) is an objective biomarker of airway inflammation. Measurements of FeNO are noninvasive, require minimal patient effort, and are easy to collect in clinical settings. The current review is a systematic review performed using PubMed, Science Direct, and Google Scholar according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) guidelines. This review discusses the entanglement of understanding FeNO measurement and supplementing existing diagnostic and assessment tools for inflammatory lung diseases. Monitoring FeNO can also help identify different asthma phenotypes within the asthma syndrome and suggest the optimal administration of inhaled corticosteroids (ICS) as elevated FeNO levels indicate ICS response. Non-adherence to ICS is a significant contributor to the failure of asthma treatment. A FeNO suppression test can be done to determine non-adherence. FeNO levels should be used with a careful history, conventional spirometric testing with bronchodilator reversibility, measures of bronchial hyperreactivity using methacholine, and other measures of eosinophilic inflammation, such as a peripheral blood eosinophil cell count. FeNO is more sensitive and specific when paired with other lung function tests.

Serial fractional exhaled nitric oxide measurements at and off work may help to identify immunologic occupational asthma in cases with complex exposures

Serial measurements of fractional exhaled nitric oxide (FeNO) at home and at work have been described to provide complementary information for the diagnosis of occupational asthma (OA) when specific inhalation challenge (SIC) is missing or doubtful. We describe two cases in which serial FeNO measurements enabled the detection of probable OA after complex exposures. A 25-year-old industrial painter with exposure to a variety of paints suffered from work-related airway symptoms for five years. Lung function was normal, and she was not atopic. SIC with hexamethylene diisocyanate was negative. A 47-year-old sign maker (screen printing, foils) suffering from work-related dyspnoea for seven years. Moderate airway obstruction, but no atopy was detectable. Due to the complex exposures SIC was not performed. Both patients performed FeNO measurements once daily during a 2–week-holiday and a subsequent 2–week-work period. In both cases elevated baseline FeNO decreased to normal (25 ppb) during holidays and increased after resuming work (case 1: 125 ppb, case 2: 45 ppb).

Methacholine and FeNO Measurement in Patients with Habit Cough.

Chronic cough is one of the most common symptoms in childhood. Making a definite diagnosis is a challenge for all pediatricians especially in patients when cough is without an organic cause like in habit cough. In this retrospective analysis, all electronic outpatient charts of the Division of Allergology and Pneumology, between January 1, 2010 and December 31, 2019 were reviewed in order to study all children with potential habit cough. All children underwent the following diagnostic algorithms, skin prick test (SPT), measurement of fractional exhaled nitric oxide (FeNO), spirometry and methacholine challenge test (MCT). The value of a normal MCT and FeNO measurement for diagnosing habit cough was investigated. The chart review revealed 482 patients with chronic cough>4 weeks. Of these, 99 (20.5%) with suspected habit cough were collected. 13 patients had to be excluded for other diagnosis and a complete data set was available in 55 patients. 33 (60.0%) of 55 patients were SPT negative and 22 (40.0%) had sensitization to common allergens. Five patients had elevated FeNO≥20 ppb and three showed severe bronchial hyperresponsiveness<0.1 mg methacholine, challenging the diagnosis of habit cough. A normal FeNO and MCT can help confirm the clinical diagnosis of habit cough. However, in patients with positive MCT and/or elevated FeNO habit cough can be present. Especially in patients with elevated FeNO and severe BHR cough variant asthma and eosinophilic bronchitis have to be ruled out.

Use of fractional exhaled nitric oxide to guide the treatment of asthma and chronic cough

Fractional exhaled nitric oxide (FeNO) is a breath biomarker that is easy to perform at the point of care in individuals 5 years or older. Elevated FeNO levels indicate increased type 2 airway inflammation, specifically increased interleukin 4/13 activity. Recent guidelines have made recommendations on the utility of FeNO measurement in the diagnosis and management of asthma. Measurement of FeNO is recommended as an adjunct to the evaluation process in patients with suspected asthma in whom the diagnosis of asthma is uncertain based on clinical presentation, spirometry, and bronchodilator challenge testing. Elevated FeNO levels are associated with an increased risk of asthma exacerbation, and FeNO suppression test can help differentiate “difficult” from “severe” asthma. High FeNO levels can predict response to anti-inflammatory therapies, including corticosteroids and certain biologics. FeNO measurement also has value in evaluation of chronic cough with increased levels suggesting a corticosteroid responsive condition such as cough-variant asthma or eosinophilic bronchitis.

Fractional exhaled nitric oxide (FeNO) and respiratory symptoms in junior high school students in Penang, Malaysia: the role of household exposure

ABSTRACT 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.

Withdrawal of inhaled corticosteroids from patients with COPD with mild or moderate airflow limitation in primary care: a feasibility randomised trial

BackgroundInhaled corticosteroids (ICS) are frequently prescribed outside guidelines to patients with chronic obstructive pulmonary disease (COPD) with mild/moderate airflow limitation and low exacerbation risk. This primary care trial explored the...

Short- and medium-term effect of inhaled corticosteroids on exhaled breath biomarkers in severe asthma

Inhaled corticosteroids (ICS) are the mainstay of therapy in asthma, but benefits vary due to disease heterogeneity. Steroid insensitivity is a particular problem in severe asthma, where patients may require systemic corticosteroids and/or biologics. Biomarkers sensitive to ICS over a short period of time could inform earlier and more personalised treatment choices. To investigate how exhaled breath biomarkers change over two-hours and one-week following monitored ICS dosing in severe asthma patients with evidence of uncontrolled airway inflammation. Patients with severe asthma and elevated fractional exhaled nitric oxide (FeNO) (⩾45 ppb, indicative of active airway inflammation) were recruited. Exhaled breath biomarkers were evaluated using (FeNO), exhaled breath temperature (EBT), particles in exhaled air (PExA) and volatile organic compounds (VOCs). Samples were collected over 2 h following observed inhalation of 1000 mcg fluticasone propionate, and at a second visit 1 week after taking the same dose daily via an inhaler monitoring device that recorded correct actuation and inhalation. Changes in parameters over 2 h were analysed by the Friedman test and 1 week by Wilcoxon’s test (p-value for significance set at 0.05; for VOCs false discovery rate q of 0.1 by Benjamini–Hochberg method applied). 17 participants (9 male) were recruited, but three could not complete PExA and two FeNO testing, as they were unable to comply with the necessary technique; complete datasets were available from 12 (9 male) with median (interquartile range) age 45 (36–59) yrs. EBT (p < 0.05) and levels of six VOCs (q < 0.1) fell over the 2 h after high dose ICS; there were no changes in FeNO or PExA. After one week of using high dose ICS, there were falls in FeNO, EBT and two VOCs (p < 0.05), but no changes in PExA. Reduction in EBT over the short and medium term after high dose ICS may reflect airway vascular changes, and this, together with the observed changes in exhaled VOCs, merits further investigation as potential markers of ICS use and effectiveness.

Evaluation of the Relationship between Fractional Exhaled Nitric Oxide (FeNO) with Indoor PM10, PM2.5 and NO2 in Suburban and Urban Schools.

Numerous epidemiological studies have evaluated the association of fractional exhaled nitric oxide (FeNO) and indoor air pollutants, but limited information available of the risks between schools located in suburban and urban areas. We therefore investigated the association of FeNO levels with indoor particulate matter (PM10 and PM2.5), and nitrogen dioxide (NO2) exposure in suburban and urban school areas. A comparative cross-sectional study was undertaken among secondary school students in eight schools located in the suburban and urban areas in the district of Hulu Langat, Selangor, Malaysia. A total of 470 school children (aged 14 years old) were randomly selected, their FeNO levels were measured, and allergic skin prick tests were conducted. The PM2.5, PM10, NO2, and carbon dioxide (CO2), temperature, and relative humidity were measured inside the classrooms. We found that the median of FeNO in the school children from urban areas (22.0 ppb, IQR = 32.0) were slightly higher as compared to the suburban group (19.5 ppb, IQR = 24.0). After adjustment of potential confounders, the two-level hierarchical multiple logistic regression models showed that the concentrations of PM2.5 were significantly associated with elevated of FeNO (>20 ppb) in school children from suburban (OR = 1.42, 95% CI = 1.17–1.72) and urban (OR = 1.30, 95% CI = 1.10–1.91) areas. Despite the concentrations of NO2 being below the local and international recommendation guidelines, NO2 was found to be significantly associated with the elevated FeNO levels among school children from suburban areas (OR = 1.11, 95% CI = 1.06–1.17). The findings of this study support the evidence of indoor pollutants in the school micro-environment associated with FeNO levels among school children from suburban and urban areas.

Fractional Exhaled Nitric Oxide as a Marker of Mucosal Inflammation in Chronic Rhinosinusitis.

Fractional exhaled nitric oxide (FeNO) is a cost-effective, noninvasive point-of-care test that has proven valuable in identifying patients with lower airway inflammation and predicting the likelihood of responsiveness to inhaled corticosteroid therapy in asthma. The utility of FeNO in upper airway disease, specifically in CRS, remains to be determined. The goal of this study was to test whether FeNO could serve as a noninvasive marker of sinonasal mucosal inflammation in CRS patients. FeNO was obtained using a nitric oxide analyzer (NIOX VERO) as well as nasal mucus, the 22-item Sinonasal Outcome Test (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Lund-Kennedy endoscopic scores concurrently in 112 CRS patients. Nasal mucus was analyzed for cytokine expression using solid-phase sandwich ELISA. Linear regression with Spearman correlation coefficient was used to determine strength of relationship between variables. CRS patients showed elevated FeNO levels with asthma (47.12 ± 5.21 ppb) or without asthma (43.24 ± 9.810 ppb). Elevated FeNO levels correlated with sinonasal mucosal inflammation, as determined by increased levels of CCL26 and TNFα in nasal mucus obtained from CRS patients. Furthermore, elevated FeNO levels selectively correlated with worsened SNOT-22 nasal symptoms (P = 0.03) and Lund-Kennedy endoscopic scores (P = 0.007), but did not correlate with UPSIT scores. FeNO levels correlated with increased sinonasal mucosal inflammation and symptom severity in CRS regardless of asthma status. FeNO measurements may serve as a quick and noninvasive marker in evaluating CRS patients.

Pulmonary function testing for the diagnosis of asthma in preschool children.

To highlight the recent evidence of the lung function techniques used in preschool children to diagnose asthma. Several techniques are available to measure lung function and airway inflammation in preschool children, including spirometry (from age 5 years), impulse oscillometry (>3 years), whole-body plethysmography (>3 years), fractional exhaled nitric oxide (FeNO) (>5 years), multiple breath washout (>3 years), structured light plethysmography (>1-2 years) and impedance pneumography (>1 years). If applicable, measuring forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio using spirometry is useful (cut-off < 80% predicted or below lower limit of normal [LLN] defined as z-score < -1.64) for diagnosing preschool asthma. For those unable to perform spirometry, whole-body plethysmography (sRaw > 1.6 kPa/s) and impulse oscillometry (Rrs and Xrs at 5 Hz z-score > 2) may be useful. Adding a bronchodilator reversibility test (FEV1 increase > 12%, sRaw decrease > 25-30%, Rrs at 5 Hz decrease > 40%) or a bronchial challenge test, for example, exercise test (FEV1 decrease > 10%), may improve the sensitivity of these tests. Elevated FeNO (>25-35 ppb) is a promising adjunctive test for diagnosing preschool asthma. With trained personnel, lung function testing can be done with high reliability even in children between 2 and 4 years of age. To avoid over and undertreatment of asthma, objective measurement of lung function is clinically important in preschool children.

New onset asthma during pregnancy: two case reports

Introduction: Asthma is the most common chronic respiratory disease during pregnancy. However, reports of new onset asthma during pregnancy are lacking. We report two cases of new onset asthma during pregnancy following respiratory tract infection, subsequently one case with M. pneumoniae infection and the other case with a combined infection with respiratory syncytial virus and rhinovirus. Case presentation: Both patients presented with the clinical features of an acute asthma exacerbation during pregnancy without a medical history of asthma. During follow up the diagnosis of asthma was supported by spirometry showing significant reversibility and elevated fractional exhaled nitric oxide (FeNO). Patients were hospitalized and received supplemental oxygen, treatment for an acute asthma exacerbation with systemic corticosteroids, high dose inhalation therapy. These therapeutic interventions subsequently led to a good outcome for the mother and newborn in both cases. Conclusions: New onset asthma should be part of the differential diagnosis in pregnant patients with respiratory symptoms, particularly in case of mycoplasma infection. Diagnosing asthma during pregnancy can be challenging. In these circumstances, additional diagnostic tests (like inflammatory biomarkers FeNO and blood eosinophils) can be helpful to support the diagnosis.

Fractional exhaled nitric oxide (FeNO) in students in Northern Thailand: associations with respiratory symptoms, diagnosed allergy and the home environment

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 (PM10 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 PM10 (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.

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). One thousand seven hundred sixteen patients with prospective data were included; 83.8%were identified as most likely (grade 3), 8.3%were identified as likely (grade 2), and 6.3%identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6%of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs6.7 years; P< .001) and worse lung function (postbronchodilator %predicted FEV1, 76.1%vs89.3%; P= .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5%vs62.9%; P= .047), to have eczema (20.8%vs8.5%; P= .003), and to use anti-IgE (32.1%vs13.4%; P= .004) and leukotriene receptor antagonists (50.0%vs28.0%; P= .011) add-on therapy. According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years.

BackgroundEarly‐life exposures to geohelminths may protect against development of wheeze/asthma and atopy.ObjectiveTo study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years.MethodsBirth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy.Results1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite‐specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non‐atopic children.ConclusionsOur data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).