Airway inflammation is a common biological response to many types of environmental exposures and can lead to increased nitric oxide (NO) concentrations in exhaled breath. In recent years, several studies have evaluated airway inflammation using fractional exhaled nitric oxide (FeNO) as a biomarker of exposures to a range of air pollutants. This systematic review aims to summarize the studies that collected personal-level air pollution data to assess the air pollution-induced FeNO responses and to determine if utilizing personal-level data resulted in an improved characterization of the relationship between air pollution exposures and FeNO compared to using only ambient air pollution exposure data.
Thirty-six eligible studies were identified. Overall, the studies included in this review establish that an increase in personal exposure to particulate and gaseous air pollutants can significantly increase FeNO. Nine out of the 12 studies reported statistically significant FeNO increases with increasing personal PM2.5 exposures, and up to 11.5% increase in FeNO per IQR increase in exposure has also been reported between FeNO and exposure to gas-phase pollutants, such as ozone, NO2, and benzene. Furthermore, factors such as chronic respiratory diseases, allergies, and medication use were found to be effect modifiers for air pollution-induced FeNO responses. About half of the studies that compared the effect estimates using both personal and ambient air pollution exposure methods reported that only personal exposure yielded significant associations with FeNO response. The evidence from the reviewed studies confirms that FeNO is a sensitive biomarker for air pollutant-induced airway inflammation. Personal air pollution exposure assessment is recommended to accurately assess the air pollution-induced FeNO responses. Furthermore, comprehensive adjustments for the potential confounding factors including the personal exposures of the co-pollutants, respiratory disease status, allergy status, and usage of medications for asthma and allergies are recommended while assessing the air pollution-induced FeNO responses.

Obesity is one of the comorbidities in patients with asthma and obese patients with asthma present with a distinct phenotype with more severe disease outcomes and reduced responsiveness to standard therapies. Although the full mechanisms of obesity‑related asthma are still not completely understood, abnormal immune responses have been demonstrated to have a critical role in asthma pathogenesis. The present review summarizes the data from clinical, epidemiological and animal studies to provide an updated understanding of the immune responses in obesity‑related asthma, as well as the effect of various factors, such as oxidative stress, mitochondrial dysfunction, genetics and epigenetics, on asthmatic inflammation. Further studies on the in‑depth mechanisms are still required to develop novel preventive and therapeutic strategies for patients with asthma combined with obesity.

The purpose of this scoping review was to identify existing clinical and basic science knowledge surrounding the effect of muscarinic receptor antagonism on allergen-induced airway responses to inform future clinical research in this area.
Multiple advanced searches were performed using the National Library of Medicine PubMed search engine. Each search began with two terms; for example, \"atropine and asthma\" or \"tiotropium and airway inflammation\". Results were then further refined to include terms such as \"allergen\" or \"ovalbumin (OVA)\". Abstracts of refined searches were reviewed for relevance to allergic asthma and allergen-induced airway responses including the early and late asthmatic responses, airway inflammation and tissue remodelling. There was no restriction regarding publication date. Reference lists of selected papers were also reviewed for relevant publications.
Nine human clinical trial publications and fourteen animal model publications were identified. In humans, single dose atropine (n=4), ipratropium (n=4) or oxitropium (n=1) administered pre-challenge produced equivocal effects on allergen-induced early asthmatic responses as reported but favored inhibition in eight of nine studies after re-analyses. Animal model investigations (n=14) showed mostly favorable results, especially with respect to airway inflammation and tissue remodelling, although two studies were negative, and one study showed a worsening in allergen induced airway inflammation following muscarinic receptor antagonism.
Existing human and animal model data suggest muscarinic receptor antagonism may be beneficial in preventing allergen induced airway responses in those with allergic asthma. Additional human research utilizing current standardized methodologies is required.

Experimental challenge studies have shown that pollen can have early and delayed effects on the lungs and airways. Here, we qualitatively and quantitatively synthesize the evidence of outdoor pollen exposure on various lung function and airway inflammation markers in community-based studies.
Four online databases were searched: Medline, Web of Science, CINAHL and Google Scholar. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were human-based studies published in English that were representative of the community. Additionally, we only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models.
We included 27 of 6551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season, eosinophilia and eosinophil cationic protein (ECP) in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age, and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age.
Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 upper and lower airway inflammation rather than a non-specific or innate inflammation. These findings can lead to the formulation of specific pollen immunotherapy for susceptible individuals. Future research should be directed towards investigating lagged associations and effect modifications using larger and more generalized populations.
CRD42020146981 (PROSPERO).

Chronic cough is defined as a daily cough that persists longer than 4 weeks. Protracted bacterial bronchitis (PBB) is a common cause of chronic wet cough in preschool children with no symptoms or signs of other specific causes, and resolution usually follows a 2-week course of an appropriate oral antibiotic. The diagnosis is mainly clinical; generally, no instrumental examinations are necessary. The most common bacteria found in the bronchoalveolar lavage (BAL) of subjects with PBB include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Nowadays, there is no certain evidence of the role of viruses in PBB pathogenesis even though different types of viruses have been detected in BAL from children with PBB. Airway malacia is commonly found in children with PBB; conversely, there is no correlation with any type of immunodeficiency. Amoxicillin-clavulanate acid is the most commonly used antibiotic, as first-line, prolonged therapy (longer than 2 weeks) is sometimes required to cough resolution. When the wet cough does not improve despite prolonged antibiotic treatment, an underlying disease should be considered. Moreover, there are several hypotheses of a link between PBB and bronchiectasis, as recent evidences show that recurrent PBB (>3 episodes/years) and the presence of H. influenzae infection in the lower airways seem to be significant risk factors to develop bronchiectasis. This underlines the importance of a close follow-up among children with PBB and the need to consider chest computerized tomography (CT) in patients with risk factors for bronchiectasis. In this brief review, we summarize the main clinical and pathogenetic findings of PBB, a disease that may be related to a relevant morbidity and decreased quality of life during the pediatric age.

Several epidemiological studies have evaluated the fractional exhaled nitric oxide (FeNO) of ambient air pollution but the results were controversial. We therefore conducted a systematic review and meta-analysis to investigate the associations between short-term exposure to air pollutants and FeNO level. We searched PubMed and Web of Science and included a total of 27 articles which focused on associations between ambient air pollutants (PM10, PM2.5, black carbon (BC), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3)) exposure and the change of FeNO. Random effect model was used to calculate the percent change of FeNO in association with a 10 or 1 μg/m3 increase in air pollutants exposure concentrations. A 10 μg/m3 increase in short-term PM10, PM2.5, NO2, and SO2 exposure was associated with a 3.20% (95% confidence interval (95%CI): 1.11%, 5.29%), 2.25% (95%CI: 1.51%, 2.99%),4.90% (95%CI: 1.98%, 7.81%), and 8.28% (95%CI: 3.61%, 12.59%) change in FeNO, respectively. A 1 μg/m3 increase in short-term exposure to BC was associated with 3.42% (95%CI: 1.34%, 5.50%) change in FeNO. The association between short-term exposure to O3 and FeNO level was insignificant (P＞0.05). Future studies are warranted to investigate the effect of multiple pollutants, different sources and composition of air pollutants on airway inflammation.

Fractional exhaled nitric oxide (FENO) is a noninvasive strategy for diagnosing and managing asthma, but limited evidence is available for the effects of FENO-guided asthma management in children. This meta-analysis aimed to evaluate the effectiveness of FENO for asthma management in children.
In total, six databases were searched, and 23 randomized controlled trials that compared the effects of FENO-guided asthma management with those not using FENO in pediatric asthma were included. Methodological quality was assessed using the Cochrane risk-of-bias tool. Data for relevant endpoints were extracted and analyzed.
Our meta-analysis of the effectiveness of FENO for asthma management in children showed that FENO-guided asthma management helped reduce the numbers of children with asthma exacerbations (risk ratio: 0.73; 95% confidence interval [CI:] 0.63-0.84; P < .0001) and the exacerbation frequency (standardized mean difference: -1.57; 95% CI: -2.25 to -0.88; P < .00001). Furthermore, it improved the predicted forced expiratory volume in 1 minute (weighted mean difference [WMD]: 3.67; 95% CI: 0.91-6.43; P = .009) and was also found to be associated with an increase of daily inhaled corticosteroid (ICS) dose (WMD: 64.17 μg; 95% CI: 53.59-74.75; P < .00001).
This meta-analysis indicated that the FENO-guided asthma management strategy could partially improve the outcomes of pediatric asthma at the expense of increased ICS use.

Introduction: Since the discovery of eosinophils in the sputum of asthmatic patients, several studies have offered evidence on their prominent role in the pathology and severity of asthma. Blood eosinophils, are a useful biomarker for therapy selection in severe asthma patients. IL-5 plays crucial role on maturation, activation, recruitment, and survival of eosinophils and constitutes an important therapeutic target for patients with severe uncontrolled eosinophilic asthma.Areas covered: This review focuses on the similarities and differences on mechanisms of action, efficacy, and safety, of two subcutaneously(SC) administered agents, the anti-interleukin(IL)-5 monoclonal antibody mepolizumab and the IL-5 receptor-α(IL-5Rα)-directed cytolytic monoclonal antibody benralizumab. All information used was collected from PubMed using keywords such as severe asthma, eosinophils, IL-5, airway inflammation, asthma exacerbations, mepolizumab, benralizumab, anti-IL5, and anti-IL5R either as single terms or in several combinations.Expert opinion: Both mepolizumab and benralizumab are promising for the treatment of severe eosinophilic asthma resulting in asthma control improvement and exacerbations reduction and can serve as steroid-sparing agents. However, since no head-to-head comparisons exist, it is unknown whether their different mechanisms of action might be related to different efficacy in specific patients\' sub-phenotypes. Long-term clinical observations will provide real-world evidence regarding their lasting effectiveness and safety.

Inflammatory airway diseases, including allergic rhinitis and asthma, are type 2 immune responses induced by antigen presenting cells and T helper cells, resulting as a consequence of great recruitment of effect cells and release of cytokines. Group 2 innate lymphoid cells were originally described as a novel population of lineage negative cells and play an important role in the onset and progression of airway inflammation by producing the critical Th2-type cytokines IL-5 and IL-13 in response to epithelial cell derived IL-25, IL-33 and thymic stromal lymphopoietin. Along with a better understanding of regulatory and effect mechanism, targeting ILC2s could be a potential therapeutic approach in inflammatory airway diseases.

We aimed to perform a systematic review of all studies with direct measurements of both airway inflammation and remodeling in the subgroup of children with repeated wheezing and/or persistent asthma severe enough to warrant bronchoscopy, to address whether airway inflammation precedes remodeling or is a parallel process, and also to assess the impact of remodeling on lung function.
Four databases were searched up to June 2017. Two independent reviewers screened the literature and extracted relevant data.
We found 526 references, and 39 studies (2390 children under 18 years old) were included. Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present in wheezers at a mean age of 12 months, but in older pre-school children (mean 2.5 years), remodeling (mainly increased reticular basement membrane [RBM] thickness and increased area of airway smooth muscle) and also airway eosinophilia was reported. This was worse in school-age children. RBM thickness was similar in atopic and non-atopic preschool wheezers. Airway remodeling was correlated with lung function in seven studies, with FeNO in three, and with HRCT-scan in one. Eosinophilic inflammation was not seen in patients without remodeling. There were no invasive longitudinal or intervention studies.
The relationship between inflammation and remodeling in children cannot be determined. Failure to demonstrate eosinophilic inflammation in the absence of remodeling is contrary to the hypothesis that inflammation causes these changes. We need reliable, non-invasive markers of remodeling in particular if this is to be addressed.