Lower Airway Inflammation Research Articles

Exposure to respirable silica contributes to lower airway inflammation in asthmatic horses.

Respirable mineral particles can induce lower airway inflammation, but the role they play in asthma of horses is unknown. Respirable mineral particles, particularly respirable silica, are an overlooked determinant of chronic lung inflammation (asthma) in horses. Twenty-three horses from an equine hospital population: 11 moderately affected (MEA), 7 severely asthmatic (SEA), and 5 control horses free from respiratory clinical signs. Prospective observational study. The quantity and quality of mineral particles found in bronchoalveolar lavage fluid (BALF) were characterized, with particular attention to silica content. Polarized light microscopy performed on cytospin slides identified intracellular birefringent particles as silica. Spectrometry-based analysis performed on whole BALF determined total mineral and silica percentage and concentration. Group-related differences in BALF mineral and silica load were investigated as well as associations with BALF cytology. Intracellular birefringent particles were increased in SEA vs MEA (median [interquartile range, IQR]), 12 [7] vs 4 [5] particles/30 high power fields [hpf], respectively; P = .01) and vs controls (4 [2] particles/30 hpf; P = .02). Total mineral concentration in BALF was similar between the groups studied, whereas silica concentration and percentage were increased in SEA vs MEA (1758 [887] particles/mL and 20 [10]% vs 867 [662] particles/mL and 8 [6]%; P = .009 and P = .001) and control group (355 [330] particles/mL and 6 [3]%; P = .0003 and P = .002). Silica load in BALF was associated with BALF neutrophilia in MEA and SEA. Respirable silica is associated with neutrophilic lower airway inflammation in horses and might contribute to asthma development.

Cytokines Measured in Nasal Lavage Compared to Induced Sputum in Patients with Mild Cystic Fibrosis

The measurement of cytokines in induced sputum and nasal lavage (NL) samples has been performed for years in people with cystic fibrosis (CF). The aim of this study was to directly compare sputum and NL samples and interpret results based on disease severity in patients who were categorized as having mild or severe lung disease. The categorization was based primarily on structural abnormalities detected on lung computed tomography and secondarily on lung function. The serum inflammatory markers neutrophil elastase (NE), IL-1β, 2, 6, 8, 10 and 17a were measured in each sputum and NL sample. Thirty-two sample pairs from 29 patients were included in this study (13 mild, 19 severe). In the patients classified as severe, many systemic inflammatory markers as well as sputum cytokines were significantly higher compared to those in the mild patients. However, all the markers measured in the NL were higher in the mild patients (p =< 0.05 for NE, IL-6 and IL-8). In addition, many cytokines in the NL correlated negatively with those in the sputum samples. Major differences in the cytokine levels were shown although the samples were obtained at the same time in the same patient. Advanced structural lung disease was closely related to systemic and lower airway inflammation, whereas preserved lung function was associated with higher levels in the NL. We hypothesize that the main part of the immune response takes place in the nasal mucosa in patients with minor pulmonary changes. Our results suggest that inflammation must be interpreted individually depending on the compartment in which it is measured. Further research is needed to accurately understand inflammatory markers measured in NL.

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

The amount of hyaluronic acid and airway remodelling increase with the severity of inflammation in neutrophilic equine asthma

BackgroundEquine asthma (EA) is a chronic lower airway inflammation that leads to structural and functional changes. Hyaluronic acid (HA) has crucial functions in the extracellular matrix homeostasis and inflammatory mediator activity. HA concentration in the lungs increases in several human airway diseases. However, its associations with naturally occurring EA and airway remodelling have not been previously studied. Our aim was to investigate the association of equine neutrophilic airway inflammation (NAI) severity, airway remodelling, and HA concentration in horses with naturally occurring EA. We hypothesised that HA concentration and airway remodelling would increase with the severity of NAI. HA concentrations of bronchoalveolar lavage fluid supernatant (SUP) and plasma of 27 neutrophilic EA horses, and 28 control horses were measured. Additionally, remodelling and HA staining intensity were assessed from endobronchial biopsies from 10 moderate NAI horses, 5 severe NAI horses, and 15 control horses.ResultsThe HA concentration in SUP was higher in EA horses compared to controls (p = 0.007). Plasma HA concentrations were not different between the groups. In the endobronchial biopsies, moderate NAI horses showed epithelial hyperplasia and inflammatory cell infiltrate, while severe NAI horses also showed fibrosis and desquamation of the epithelium. The degree of remodelling was higher in severe NAI compared to moderate NAI (p = 0.048) and controls (p = 0.016). Intense HA staining was observed in bronchial cell membranes, basement membranes, and connective tissue without significant differences between the groups.ConclusionThe release of HA to the airway lumen increases in naturally occurring neutrophilic EA without clear changes in its tissue distribution, and significant airway remodelling only develops in severe NAI.

Evaluation of bronchoalveolar lavage fluid from donkeys using four different cytological stains: A pilot study

Bronchoalveolar lavage fluid (BALF) cytology is used for the diagnosis of non-infectious lower airway inflammation in equids. Discrepancies have been reported in the differential cell count when different staining methods were used both in humans and horses. The objective of this study was to compare the results of BALF cytology in donkeys using four different staining methods: modified May-Grunwald Giemsa (mMGG), Diff-Quick (DQ), Toluidine blue (TB) and Perls Prussian blue (PPB). Nine healthy Amiata female donkeys were enrolled. The BAL procedure was performed as previously described and pairs of cytocentrifuged BALF slides were stained with each method. No differences between mMGG and DQ were found for macrophages, neutrophils, and eosinophils, while differences were found in mast cell count between DQ vs.TB, but not between mMGG vs. DQ or mMGG vs. TB. Finally, no differences were obtained in the differential count for hemosiderophages comparing mMGG, DQ and PPB. The mMGG appears to be an excellent stain for the identification of all possible cell types, including mast cells in the BALF of donkeys. DQ, if used alone, may lead to inappropriate identification of mast cells. These results are consistent with the literature on BALF staining methods in horses.

Sustained control of recalcitrant chronic spontaneous urticaria after initiation of inflammatory airway diseases treatment: two case reports

BackgroundCurrent classification of chronic urticaria is primarily based on clinical presentation of skin manifestations. Hence, therapeutic treatment is primarily aimed locally for immediate symptom relief. We reason that limiting therapeutic strategies to the skin pathology might be inadequate since cellular activation and inflammation might be triggered remotely.Case presentationIn this series two patients had exhausted all current treatments for recalcitrant urticaria but remained symptomatic. The first case was 26-year-old Caucasian female and the second was 63-year-old African American female. Both cases had frequent breakthrough urticaria requiring frequent pulsating courses of prednisone to control urticaria despite treatment with omalizumab and antihistamines. When inflammatory airway disease was discovered and managed with inhaled corticosteroid, urticaria is controlled much faster without the need of high dose immunosuppression over several years of observation. Coincidentally, autoimmune thyroiditis and anti-immunogobulin-E immunoglobulin-G titers dropped significantly in one case with sustained inhaled corticosteroid therapy.ConclusionsWe suggest a novel approach of controlling remote epithelial site inflammation in these two cases that resulted in sustained-control of urticaria symptoms without the need for systemic corticosteroids or immunosuppressant. The changes of autoimmune antibodies might be the consequences of tolerance breaking from chronic lower airway inflammation as observed in other epithelial inflammatory condition like in celiac disease and rheumatoid arthritis.

Impact of Montelukast on Allergic Rhinitis and Asthma as Emerging New Treatment Option

Background: AR (allergic rhinitis) is a condition that causes chronic nasal mucosal inflammation. Among the regional signs of AR are sneezing, rhinorrhea, nasal discomfort, and nasal congestion. AR places a considerable financial and social impact on both the person with AR and society. There is mounting evidence that AR may elevate inflammatory mediators throughout the body and raise the chance of developing asthma. Aim: To determine the degree to which Montelukast altered the symptoms and signs of allergic rhinitis (AR) and asthma, as well as to estimate the proportion of participants who were adversely affected. The absolute eosinophil count and five essential asthma and allergic rhinitis symptoms were assessed before and after therapy. Method: This was a randomized trial. This experiment at the Lahore General Hospital involved 204 participants with asthma and allergic rhinitis. Participants received either (budesonide) BD (256 mg) with (montelukast) MNT (10mg) + MNT for two weeks, or BD alone (256 mg). The data was entered and analysed in SPSS 23. Results:However, when compared to BD alone, BD + MNT demonstrated noticeably greater improvements in nasal blockage and itching. Both treatments greatly lessened the five primary symptoms as compared to the baseline. After two weeks of treatment, absolute eosinophil counts in BD + MNT significantly surpassed BD. Practical Implication: Asthma and allergic rhinitis are major problems nowadays. This investigation will help find better answers to this problem. BD+ MNT is a more successful treatment for this illness. Conclusion:BD + MNT therapy may be more efficient overall than BD monotherapy for those with asthma and allergic rhinitis, especially in lowering nasal obstruction, itching, and subclinical lower airway inflammation. The absolute eosinophil count can also be used to monitor a patient's response to treatment for allergic rhinitis. Keywords: Asthama, budesonide, montelukast, and allergic rhinitis. Key words: Montelukast, allergic rhinitis, Asthma, Emerging New Treatment Option

Sleep Respiratory Disorders in Children and Adolescents with Cystic Fibrosis and Primary Ciliary Dyskinesia.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.

Exhaled Nitric Oxide and Olfactory Dysfunction in Patients with Asthma: Association with Chronic Rhinosinusitis.

Objectives: Olfactory dysfunction is a clinical sign that is important to detect with coexistent upper airway comorbidities in patients with asthma. This study aimed to investigate the etiology of olfactory dysfunction in patients with asthma and the relationship between fractional exhaled nitric oxide (FeNO) levels. Materials and Methods: This study included 47 asthma patients who were evaluated for olfactory dysfunction at Hiroshima University Hospital between 2012 and 2020. The etiologies of olfactory dysfunction were evaluated, and they were classified according to the FeNO levels of patients with asthma. Results: Olfactory dysfunction was observed in 30 patients with asthma, with chronic rhinosinusitis (77%) being the most prevalent etiology. Eosinophilic chronic rhinosinusitis (ECRS) was the most prevalent etiology of olfactory dysfunction in asthma patients with high FeNO levels (≥25 ppb), while non-eosinophilic chronic rhinosinusitis (NCRS) was the most prevalent etiology in asthma patients with low FeNO levels (<25 ppb). Additionally, the prevalence of ECRS was significantly higher in asthma patients with olfactory dysfunction and high FeNO levels (74%) than in those with either high FeNO levels or olfactory dysfunction and those with low FeNO levels and no olfactory dysfunction (12% and 9%, respectively). Conclusions: We found that ECRS was the predominant cause of olfactory dysfunction in patients with high FeNO levels, while NCRS was more common in those with low FeNO levels. The present study showed that both ECRS and NCRS are common etiologies of olfactory dysfunction in patients with asthma. Additionally, this study supports the link between upper and lower airway inflammation in patients with asthma complicated with olfactory dysfunction.

The unified airway hypothesis: evidence from specific intervention with anti-interleukin-5 biologic therapy.

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and interleukin (IL)-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP] and non-steroidal anti-inflammatory drug exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision-making.

Can we apply biomarkers in the management of non-steroidal anti-inflammatory drug exacerbated respiratory disease?

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by adult-onset asthma, chronic rhinosinusitis with nasal polyps (CRSwNPs), and aspirin/NSAID hypersensitivity, presenting recurrent asthma exacerbation and poor clinical outcomes. Patients with NERD have heterogeneous clinical phenotypes/endotypes, and the management of NERD remains challenging. Dysregulation of arachidonic acid (AA) metabolism and persistent eosinophilic airway inflammation are the major pathogenic mechanisms in the upper and lower airways of NERD. To date, increased levels of urinary leukotriene E4 (uLTE4) [a terminal metabolite of the lipoxygenase (LOX) pathway] have been the most relevant biomarker for NERD. It is demonstrated that mast cells, platelets, and epithelial cells can amplify upper and lower airway inflammation in NERD, and several potential biomarkers based on these complicated and heterogeneous mechanisms have been suggested. This review summarizes potential biomarkers for application in the management of NERD.

Associations between Medical Disorders and Racing Outcomes in Poorly Performing Standardbred Trotter Racehorses: A Retrospective Study.

Poor performance in racehorses is commonly associated with subclinical diseases. This study aims to evaluate the associations between medical disorders and racing results in Standardbred trotters. The clinical records of 248 poorly performing Standardbreds were retrospectively reviewed, and their racing results were extracted from an online database, concerning the periods 3 months before and 6 months after hospitalization and the entire lifetime. Generalized linear models were used to evaluate the effects of different disorders on racing outcomes. Airway neutrophilia was associated with limiting lifetime starts and wins pre- and post-hospitalization, while mastocytosis was associated with less wins in the post-hospitalization period. Therefore, lower airway inflammation showed both short- and long-term impacts on racing performance. Severe upper airway obstructions and gastric ulcers showed associations with less placings in the post-discharge period but no long-term influence on performance. The significance of exertional rhabdomyolysis was indeterminable, yet interference with the number of starts in the post-discharge period was reported and associated with lower total career earnings. Exercise-induced pulmonary hemorrhage and cardiac arrhythmias were not associated with worse racing outcomes: therefore, their role in poor performance remains unclear.

Asthma: The Use of Animal Models and Their Translational Utility

Asthma is characterized by chronic lower airway inflammation that results in airway remodeling, which can lead to a permanent decrease in lung function. The pathophysiology driving the development of asthma is complex and heterogenous. Animal models have been and continue to be essential for the discovery of molecular pathways driving the pathophysiology of asthma and novel therapeutic approaches. Animal models of asthma may be induced or naturally occurring. Species used to study asthma include mouse, rat, guinea pig, cat, dog, sheep, horse, and nonhuman primate. Some of the aspects to consider when evaluating any of these asthma models are cost, labor, reagent availability, regulatory burden, relevance to natural disease in humans, type of lower airway inflammation, biological samples available for testing, and ultimately whether the model can answer the research question(s). This review aims to discuss the animal models most available for asthma investigation, with an emphasis on describing the inciting antigen/allergen, inflammatory response induced, and its translation to human asthma.

Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma.

Equine asthma is a naturally occurring lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling, and lower airway inflammation. Asthma is currently divided into two major groups, mild to moderate asthma (mEA) and severe asthma (sEA), but further subtyping by phenotype (i.e., clinical presentation) and/or endotype (i.e., cellular mechanisms) may be warranted. For this study, we were interested in further investigation of cellular and inflammatory characteristics of EA, including airway mast cells. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. We hypothesized that there would be significant differences in the cellular mast cell phenotypes (i.e., mucosal vs. connective tissue) and cytokine profiles in the BALF of asthmatic vs. healthy horses and across asthma groups. We assert these characteristics may inform additional subtypes of equine asthma. Adult horses were recruited from the institution's teaching herd and clinical caseload. Mast cell protease gene expression of the BALF cellular component and multiplex bead immunoassay for cytokine concentrations in the BALF supernatant were investigated. Airway mast cells primarily expressed tryptase, with low levels of chymase. No significant changes in protease expression were detected across groups. Horses with severe asthma had increased TNF-α, CXCL-8, and IFN-γ concentrations in BALF supernatant. Multidimensional analysis demonstrated healthy and mEA horses have overlapping characteristics, with sEA separating from the other groups. This difference was primarily due to BALF neutrophil and lymphocyte concentrations. These study results further inform understanding of EA immunopathology, and future studies designed to investigate asthma phenotypes and endotypes. Ultimately, a better understanding of these groups could help identify novel therapeutic strategies.

Heart rate variability during high-speed treadmill exercise and recovery in Thoroughbred racehorses presented for poor performance.

Heart rate variability (HRV) analysis measures the inter-beat interval variation of successive cardiac cycles. Measurement of these indices has been used to assess cardiac autonomic modulation and for arrhythmia identification in exercising horses. To report HRV indices during submaximal exercise, strenuous exercise and recovery, and explore relationships with clinical conditions (arrhythmias, lameness, equine gastric ulcer syndrome [EGUS], lower airway inflammation and upper respiratory tract obstructions [URTOs]) in Thoroughbred racehorses. Retrospective, observational cross-sectional study. One hundred and eighty Thoroughbred horses underwent a treadmill exercise test with simultaneous electrocardiographic recording. Time-domain HRV indices (standard deviation of the R-R interval [SDRR]; root mean square of successive differences [RMSSD]) were derived for submaximal and strenuous exercise and recovery segments. Clinical conditions (arrhythmia [during each phase of exercise], lameness, EGUS, lower airway inflammation and URTO) were assigned to binary categories for statistical analysis. Relationships between selected HRV indices and the clinical conditions were explored using linear regression models. During submaximal exercise, lameness was associated with decreased logRMSSD (B=-0.19 95% confidence interval [CI] -0.31 to -0.06, p=0.006) and arrhythmia was associated with increased logRMSSD (B=0.31 95% CI 0.01-0.608, p=0.04). During strenuous exercise, arrhythmia was associated with increased HRV indices (logSDRR B=0.51 95% CI 0.40-0.62, p < 0.001; RMSSD B=0.60 95% CI 0.49-0.72, p < 0.001). During recovery, arrhythmia was associated with increased HRV indices (logSDRR B=0.51 95% CI 0.40-0.62, p < 0.001, logRMSSD B=0.60 95% CI 0.49-0.72, p < 0.001). The main limitations of this retrospective study were that not every horse had the full range of clinical testing, therefore some horses may have had undetected abnormalities. The presence of arrhythmia increased HRV in both phases of exercise and recovery. Lameness decreased HRV during submaximal exercise.

Impact of Lower Airway Inflammation on Fitness Parameters in Standardbred Racehorses.

Mild-moderate equine asthma (MEA) is a common respiratory disorder among racehorses, characterized by lower airway inflammation. Although it is generally agreed that MEA causes poor performance, contrasting results have been reported about the effects of tracheal mucus and the leukocyte populations of the bronchoalveolar lavage (BAL) on performance. This study aims to investigate the associations between airway inflammation and fitness parameters measured during an incremental treadmill test on Standardbred racehorses. For this purpose, the clinical records of 116 Standardbreds subjected to a diagnostic protocol for poor performance were retrospectively reviewed. Parametric and nonparametric statistics were used to evaluate the relationships between endoscopic scores, BAL cytological results, and fitness parameters. Moreover, horses were divided into MEA and non-MEA groups and into neutrophilic, eosinophilic-mastocytic, and mixed MEA groups; fitness parameters were compared between groups. Neutrophils percentages were inversely correlated with the speed at a heart rate of 200 bpm, the speed and heart rate at a plasma lactate concentration of 4 mmol/L (VLa4 and HRLa4), and the maximal speed, while they were positively correlated with higher lactate concentrations. Moreover, significant differences were detected between different MEA subtypes concerning VLa4, HRLa4, and lactate concentrations. These results suggest that airway neutrophilic inflammation impairs athletic capacity in Standardbreds.

Equine asthma: managing the environment

Equine asthma is an umbrella term defined by nonseptic lower airway inflammation. Currently there are two broad categories, namely mild to moderate equine asthma (formerly known as inflammatory airway disease) and severe equine asthma (formerly known as recurrent airway obstruction or heaves). Environmental challenge is involved in the aetiopathogenesis of both these subcategories. Much of this challenge, and the part that we can control, is provided by the organic dust associated with the stabling of horses. This article reviews the available evidence relating to the environmental management of equine asthma and tries to relate this to practical options for providing a low-dust environment.

Effect of the Administration of a Nutraceutical Supplement in Racehorses with Lower Airway Inflammation.

Simple SummaryThe study of non-pharmacological products that could have a beneficial action on the respiratory system of the horse may have a great impact on the welfare and performance of equine athletes. As a matter of fact, young racehorses can be affected by a mild–moderate form of equine asthma (MEA), that can reach a prevalence of 80%, and pharmacological treatments during racing days are almost always forbidden. This study aimed to evaluate the efficacy of the administration of a feed supplement, composed of several nutraceutical herbs, in the treatment of lower airway inflammation. This product was administered to seven racehorses with MEA, while five horses were used as control. After 21 days, horses treated with the supplement showed a lower degree of clinical signs and lower mucus accumulation in the trachea, compared to controls. For this reason, the supplement was shown to be effective in controlling lower airway inflammation, and its use as an adjunctive treatment for MEA may deserve to be evaluated.Mild–moderate equine asthma (MEA) is a chronic inflammatory disorder of the lower airways of the horse, characterized by tracheal mucus accumulation, cough and poor performance. The therapeutic approach is based on pharmacological treatment and environmental management. Moreover, the efficacy of the administration of antioxidant molecules has been reported. The aim of the present study was to evaluate the effect of the administration of a commercial nutraceutical supplement, composed of several herbal extracts, on lower airway inflammation in racehorses. Twelve Thoroughbreds affected by MEA were selected. All horses underwent a clinical examination with assignment of a clinical score, airway endoscopy and cytological examination of bronchoalveolar lavage fluid. In seven horses, the supplement was administered for 21 days in association with environmental changes, while in five horses only environmental changes were performed. All procedures were repeated at the end of the study. Data concerning the clinical score, the endoscopic scores and the cytology at the beginning and at the end of the study were statistically compared. Data showed a significant reduction (p < 0.0156) of the clinical score and a significant reduction (p < 0.0156) of the tracheal mucus score. The results showed the beneficial effect of the supplement on mild–moderate lower airway inflammation, probably due to its antioxidant activity.

Relationship between exhaled nitric oxide and biomarkers of atopy in children and adolescents with allergic rhinitis

IntroductionMeasurement of the exhaled nitric oxide fraction (FeNO) has been proposed as an indirect and non-invasive method to detect eosinophilic airway inflammation. Allergic rhinitis (AR) is frequently associated with high levels of FeNO. Allergic sensitization can contribute to the recruitment of eosinophils in the airway and the consequent increase in FeNO. ObjectiveTo correlate FeNO values with inflammatory and atopic sensitization biomarkers in patients with AR. Patients and methodsObservational, analytical, cross-sectional study. Children and adolescents with AR without asthma were included. FeNO, blood eosinophil count, total serum IgE were determined and skin tests with aeroallergens were performed by calculating the scores for PPC1 (number of positive allergens), STS2 (sum of millimeters of positive papules) and the atopy index (ratio between STS2/STS1). Spearman's correlation test was used between FeNO and variables of inflammation and atopy. ResultsTwenty-eight patients between 6 and 17 years old were included. There was a significant positive correlation between FeNO and blood eosinophils (r=.38; p=.047) and between FeNO and the atopy index (r=.40; p=.03). No correlation was found between FeNO and total serum IgE (r=.24; p=.21), STS1 (r=.20; p=.32) and STS2 (r=.34; p=.08). ConclusionIn children and adolescents with AR, FeNO was correlated with the atopy index and the blood eosinophil count. These last biomarkers could be used as alternatives for FeNO as biomarkers of lower airway inflammation in patients with AR.

HSP70 upregulation in nasal mucosa of symptomatic children with allergic rhinitis and potential risk of asthma development

Allergic rhinitis and asthma are the most common causes of chronic inflammation of the upper and lower airways in childhood. However, a nasal biomarker that can link to pulmonary inflammation is yet to be found. The present paper aims to investigate the possible role in inflammation of two inducible 70-kDa Heat Shock Proteins (HSP70) members, HSPA1A/B and HSPA6, in nasal mucosa cells of allergic children through their mRNA expression analysis, and their correlation to both spirometric and FeNO values. The relationship between FeNO in lower airways and ∆Cts of HSPA1A/B in nasal mucosa seems to be influenced by clinical symptoms regardless of age, sex, and sensitization patterns. Therefore, HSP70 expression, as well as FeNO levels, could have a predictive capability to identify lower airways inflammation and thus to recognize rhinitic children having a potential risk of asthma development.