Lower Airway Inflammation Research Articles

Tumor necrosis factor-alpha protein concentrations in bronchoalveolar lavage fluid from healthy horses and horses with severe equine asthma

The objective of this study was to determine if TNF-α protein concentration differs in bronchoalveolar lavage fluid (BALF) obtained from healthy horses, horses with naturally occurring exacerbations of severe equine asthma and horses in remission from severe equine asthma. Tumor necrosis factor-alpha (TNF- α) protein concentrations were determined in BALF by commercial equine ELISA. Horses with naturally occurring exacerbation of severe equine asthma were found to have significantly lower BALF TNF-α protein concentrations than healthy horses (p = 0.0026). There was no significant difference in BALF TNF-α concentration between horses in exacerbation and remission from disease, but there was a decrease in median TNF-α concentration between healthy horses and horses with clinical exacerbation of severe equine asthma. These findings suggest, that similar to human asthma, the role of TNF-α in chronic lower airway inflammation of horses may differ between disease phenotypes and disease state. Furthermore, the method with which TNF-α is measured (mRNA expression vs. protein concentration) may affect results when studying the role of TNF-α in horses with severe equine asthma.

Association of neutrophil morphology with bacterial isolates in equine tracheal wash samples.

Tracheal wash sample neutrophilia is common in lower airway inflammation of various causes; however, relevance of cytomorphological features to culture of bacterial pathogens has not been established. To investigate whether the presence of nondegenerate or degenerate neutrophils in tracheal washes is associated with culture of bacteria and, if so, whether this is influenced by age or temporal factors. Cross-sectional study. Tracheal wash samples submitted to Rossdales LLP from 1/1/2013 to 31/7/2015 were evaluated using set criteria. Neutrophilia and degenerate neutrophilia (graded ≥2/4 on Rossdales cytological scale [0-4]) were analysed in relation to bacterial isolates considered potentially pathogenic in respiratory disease. Statistical analyses included multivariable logistic regression to identify associations between two separate outcomes: 1) the presence of neutrophilia compared with no neutrophilia and 2) the presence of degenerate neutrophilia compared with nondegenerate neutrophilia and four independent variables. Sufficient data for inclusion in the multivariable model for nondegenerate neutrophilia were available from 1100 horses. Culture of potentially pathogenic bacteria was associated with increased odds of degenerate neutrophilia compared with samples with negative culture (OR 4.5, 95% CI 3.1, 6.4, P-value<0.001). Horses over 9 years old had lower odds of having degenerate neutrophilia than those aged 1-3 years (OR 0.6, 95% CI 0.4, 0.9, P-value<0.02). In the spring/summer, horses had reduced odds of a degenerate neutrophilia compared with winter (OR 0.4, 95% CI 0.3, 0.7, P-value <0.001). The study relied on routine laboratory submissions, with no control over sample collection or submitted clinical history. Cytological evaluation of tracheal washes should include cytomorphological features of the neutrophil response. The presence of degenerate neutrophils, especially in young horses, indicates added value of culture and sensitivity for antimicrobial therapeutics. The absence of degenerate changes, in combination with clinical factors, can help support diagnosis of a nonseptic cause of airway neutrophilia.

CpG-ODNs and Budesonide Act Synergistically to Improve Allergic Responses in Combined Allergic Rhinitis and Asthma Syndrome Induced by Chronic Exposure to Ovalbumin by Modulating the TSLP-DC-OX40L Axis.

The experimental model of combined allergic rhinitis and asthma syndrome (CARAS) has shown that CpG oligodeoxynucleotides (CpG-ODNs) are potential inhibitors of type 2 helper cell-driven inflammatory responses. Currently available CpG-ODNs modestly inhibit allergic responses in CARAS, while a combination strategy for upper airway treatment by co-administration of CpG-ODNs and glucocorticoids may show good efficacy. This study aimed to assess the therapeutic effects of CpG-ODNs combined with budesonide (BUD) on upper and lower-airway inflammation and remodeling in mice with CARAS induced by chronic exposure to ovalbumin (OVA), exploring the possible underlying molecular mechanisms. A BALB/c mouse model of chronic CARAS was established by systemic sensitization and repeated challenge with OVA. Treatment with CpG-ODNs or BUD by intranasal administration was started 1h after OVA challenge. Then, nasal mucosa and lung tissues were fixed and stained for pathologic analysis. The resulting immunologic variables and TSLP-DC-OX40L axis parameters were evaluated. Both CpG-ODNs and BUD intranasal administration are effective on reducing Th2-type airway inflammation and tissue remodeling. Co-administration of CpG-ODNs and BUD was more effective than each monotherapy in attenuating upper and lower-airway inflammation as well as airway remodeling in chronic CARAS. Notably, combination of CpG-ODNs with BUD modulated the TSLP-DC-OX40L axis, as demonstrated by decreased TSLP production in the nose and lung, alongside decreased TSLPR and OX40L in DC. Intranasal co-administration of CpG-ODNs and BUD synergistically alleviates airway inflammation and tissue remodeling in experimental chronic CARAS, through shared cellular pathways, as a potent antagonist of the TSLP-DC-OX40L axis.

Bronchiectasis, Chronic Suppurative Lung Disease and Protracted Bacterial Bronchitis

Bronchiectasis is a structural airway disease characterized by dilated bronchi and bronchioles due to severe or recurrent lower airways inflammation. Bronchiectasis can occur as a result of chronic pulmonary aspiration. Bronchiectasis may also be associated with a wide variety of systemic diseases, which should be considered in the differential diagnosis. Children with bronchiectasis typically have a chronic or recurrent productive cough and carry a significant burden of disease with a considerable impact on quality of life. The diagnosis of bronchiectasis is made by high-resolution chest computerized tomography. Aggressive management of bronchiectasis is necessary to reduce the daily symptom burden and frequency of exacerbations. Chronic suppurative lung disease may be a precursor to bronchiectasis, only lacking the defining radiographic features of bronchiectasis. Children with chronic suppurative lung disease may have the same symptoms as children with bronchiectasis and should be treated similarly. Protracted bacterial bronchitis is defined as a cough lasting at least four weeks that responds to antibiotic therapy. Protracted bacterial bronchitis may occur following a viral respiratory tract infection. Protracted bacterial bronchitis can be treated with a prolonged course of empiric antibiotics. Further evaluation is necessary if a child with suspected protracted bacterial bronchitis does not adequately respond to antibiotics as chronic suppurative lung disease or bronchiectasis must be considered.

Asthma-COPD Overlap Phenotypes and Smoking :Comparative features of asthma in smoking or non-smoking patients with an incomplete reversibility of airway obstruction

ABSTRACTThe development of COPD features, such as an incomplete reversibility of airway obstruction (IRAO), in smoking or non-smoking asthmatic patients, a condition often named Asthma-COPD Overlap (ACO), has been recognized for decades. However, there is a need to know more about the sub-phenotypes of this condition according to smoking.This study aimed at comparing the clinical, physiological and inflammatory features of smoking and non-smoking asthmatic patients exhibiting IRAO.In this cross-sectional study, patients with an IRAO with (ACO, ≥20 pack-years) or without (NS-IRAO, <5 pack-years) significant smoking history completed questionnaires about asthma control (ACQ, score 0–6, 6 = better score) and quality of life (AQLQ, score 1–7, 1 = better score) and performed expiratory flows, lung volume and carbon monoxide diffusion capacity measurements. Blood sampling and induced sputum were obtained for systemic and lower airway inflammation assessment.A total of 115 asthmatic patients were included (75 ACO: age 61 ± 10 years, 60% women and 40 NS-IRAO: age 64 ± 9 years, 38% women). ACO patients had worse asthma control scores (1.8 ± 0.9 vs 1.4 ± 0.9, P = 0.02) and poorer asthma quality of life (5.3 ± 1.0 vs 5.9 ± 1.0, P = 0.003). In addition, ACO had higher residual volume (145 ± 45 vs 121 ± 29% predicted, P = 0.008) and a lower carbon monoxide diffusing capacity corrected for alveolar volume (90 ± 22 vs 108 ± 20% predicted, P = 0.0008). No significant differences were observed in systemic or lower airway inflammation.In conclusion, in smokers and non-smokers, the presence of IRAO in asthmatics is associated with different phenotypes that reflect the addition of smoking-induced changes to asthma physiopathology.

Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with lower airway disease. However, only few studies of CRSwNP from outside secondary/tertiary care centres have been published. We recently reported an asthma frequency of 44% and 65% in primary and secondary care patients respectively. Therefore, we hypothesise that inflammation of the lower airways could be present in all CRSwNP patients, even without asthma. Here, we assessed the degree of lower and upper airway inflammation using exhaled and nasal nitric oxide (NO) in primary care CRSwNP patients with and without asthma. Fifty-seven patients who met the EPOS criteria for CRSwNP were prospectively recruited from primary care ear, nose and throat clinics. Nasal endoscopy was performed by an ear, nose and throat specialist upon enrolment. Additionally, 30 healthy controls were enrolled. Expiratory and nasal NO measurements and thorough pulmonary evaluation were performed. Pulmonary disease was diagnosed by a respiratory physician. Fifty-nine percent of CRSwNP patients with asthma showed elevated expiratory NO; the same was seen in 29% of non-asthmatic CRSwNP patients. Compared with controls, a high level of exhaled NO was significantly more prevalent in CRSwNP irrespective of asthma-status. Nasal NO was significantly lower in patients with CRSwNP compared with controls. Subclinical eosinophilic lower airway inflammation is common in CRSwNP in the primary sector, even in the absence of asthma.

Associations of Serum 25(OH)D Concentrations with Lung Function, Airway Inflammation and Common Cold in the General Population.

Vitamin D is hypothesized to have a beneficial effect on lung function and respiratory infections. The aim of this study was to assess the relationship of serum 25-hydroxyvitamin D (25(OH)D) concentrations with lung function, airway inflammation and common colds. We performed a cross-sectional analysis in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. We included participants with measurements of serum 25(OH)D, Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Fractional Exhaled Nitric Oxide (FeNO), and data on self-reported common colds (n = 6138). In crude associations, serum 25(OH)D was positively associated with FEV1 and FVC, and negatively with FeNO and the occurrence of a common cold. After adjustment for confounders, however, these associations disappeared. Stratified analyses showed that Body Mass Index (BMI) was an effect modifier in the relationship between serum 25(OH)D and FEV1, FVC and FeNO. In obese participants (BMI ≥ 30 kg/m2), 10 nmol/L higher 25(OH)D was associated with 0.46% predicted higher FEV1 (95% Confidence Interval: 0.17 to 0.75), 0.46% predicted higher FVC (0.18 to 0.74), and 0.24 ppb lower FeNO (−0.43 to −0.04). Thus, in the total study population, 25(OH)D concentrations were not associated with lung function, airway inflammation and common colds. In obese participants, however, higher 25(OH)D concentrations were associated with a better lung function and lower airway inflammation.

Impact of School Air Quality on Children's Respiratory Health.

Background:Asthma is common in children with indoor pollutants influencing the development of the disease. Since children spend most of their time outside their homes within the school environment, school indoor air quality can directly influence their respiratory health.Aims:This study aims to analyze the indoor and outdoor air quality of Maltese schools and if an association exists between indoor pollutants and respiratory health in children.Settings and Design:Five primary schools were selected with 9- to 11-year-old students participating.Materials and Methods:Standardized health questionnaires and lung function tests were utilized. Indoor and outdoor air sampling together with traffic counts were carried out.Statistical Analysis Used:SPSS version 21 was used and the Chi-squared, logistic regression, and Pearson's correlation were used.Results:The mean indoor PM 2.5 level of 17.78 μg/m3 and CO (9.11 ppm) exceeded World Health Organization thresholds. Indoor ozone levels exceeded the mean European school's indoor ozone concentration of 8 μg/m3. High exposure to formaldehyde, NO2, and ozone was associated with atopy in children. Heavy vehicles passing near the schools were associated with current wheezing (P < 0.001) but not nocturnal cough (P = 0.34).Conclusions:School indoor and outdoor environment has a direct impact on children's respiratory health. This study has identified significant associations between high exposures to indoor air pollutants, school characteristics, and upper and lower airway inflammation.

Histopathological Assessment of Airway Inflammation and Remodeling in Lungs of Donkeys

Donkeys in developing countries are usually used in transport and agriculture. They usually receive less attention compared to horses and little information is available about the pathology of many diseases including respiratory ones. Therefore, this study was performed to investigate the incidence and pathological finding of airway inflammation in donkeys. A 73 of variable ages and sexes donkeys were used in the current study. They were subjected to postmortem examination of the lungs. Histopathological examination of lungs and lesion scoring for 7 variables including epithelial hyperplasia, Goblet cell metaplasia, basement membrane thickening, submucosal inflammatory cells, smooth muscle hyperplasia, peribronchiolar fibrosis and hemosiderin in small sized bronchi and bronchioles was performed. Presence of cartilaginous degeneration and bronchial associated lymphoid follicles (BALT) was also recorded. Airway inflammation in donkeys were reported in 87.6% of examined donkeys.Lesion scoring was high in epithelial hyperplasia (1.96 ± 0.08) smooth muscle hyperplasia (1.81 ± 0.09) and inflammatory cells infiltration (1.5 ± 0.08). Other variables had less severity. Peribronchial fibrosis was observed in 17 (26.56%) cases affected with a mild severity (0.32 ± 0.07). Cartilage degeneration and loss was found in 6 cases (9.37%) and BALT hyperplasia was found in 9 cases (14.06%). Presence of hemosiderin pigment around bronchioles was less frequently observed. The donkeys exhibits a high incidence of lower airway inflammation.

Characteristics of lower airway inflammatory changes in the minimal persistent inflammation of allergic rhinitis in mice

ABSTRACTObjective: This study aims to establish an experimental mouse model of minimal persistent inflammation (MPI), observe the features of inflammation and hyper-responsiveness of the upper/lower airways, and explore the relationship between inflammation and hyper-responsiveness in the upper/lower airways. Methods: Sixty-four female BALB/c mice were randomly divided into four groups: allergic rhinitis (AR) group as positive control, MPI group, negative control group and blank control group. Mice were given high and low-concentrated ovalbumin solution after basic and intensive sensitization to establish AR model and MPI model. Nasal mucosa and lung tissues were stained to observe eosinophil infiltration, goblet cell hyperplasia, and expression of intercellular adhesion molecule 1 (ICAM-1). Airway hyper-responsiveness was assessed. Levels of specific immunoglobulin E (sIgE), interleukin (IL)-4 and IL-5 in peripheral blood, nasal lavage fluid (NLF), and bronchoalveolar lavage fluid (BALF) were detected by Enzyme-linked immunosorbent assay. Results: The eosinophil infiltration and expression of ICAM-1 on nasal mucosa and in lung tissues in the AR and MPI groups were significantly elevated compared to control groups. Goblet cells count increased only in the nasal mucosa and not in lung tissues. Eosinophil and neutrophil count of NLF and BALF in the AR and MPI groups increased significantly compared to control groups. Level of IL-4 did not increase significantly, but sIgE and IL-5 did. Conclusions: Mice in the MPI status exhibits lower airway inflammation and hyper-responsiveness with increase in eosinophil count, goblet cells, ICAM-1, IL-4, and IL-5. These results provide further evidence for the importance of MPI of AR in lower airway diseases.

Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and -9 in horses with chronic airway inflammation.

OBJECTIVE To examine whether expression of extracellular matrix metalloproteinase inducer (EMMPRIN) can be detected in equine lungs and whether it correlates with matrix metalloproteinase (MMP)-2 and -9 expression in bronchoalveolar lavage fluid (BALF) of horses with chronic inflammation of the lungs (ie, lower airway inflammation [LAI]). ANIMALS 29 horses with signs of chronic respiratory tract disease, which were classified as the LAI (n = 17) and LAI with respiratory distress (RDLAI [12]) groups, and 15 control horses. PROCEDURES BALF, tracheal aspirate, and blood samples were obtained, and EMMPRIN expression was determined from BALF cells and RBCs by use of western blotting. Activities of MMP-2 and -9 were determined with zymography. RESULTS Expression of EMMPRIN protein was identified in BALF cells of all horses. Expression of EMMPRIN protein was highest for the RDLAI group and was correlated with MMP-2 and -9 protein expression, MMP-9 gelatinolytic activity, and airway neutrophilia. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that EMMPRIN was involved in the pathophysiologic processes of asthma in horses. However, additional studies of horses and other species are warranted to elucidate the regulation of EMMPRIN expression in asthmatic lungs.

Glycolysis and the Hexosamine Biosynthetic Pathway as Novel Targets for Upper and Lower Airway Inflammation.

Glycolysis is a process that rapidly converts glucose to lactate to produce adenosine triphosphate (ATP) under anaerobic conditions and occurs in all eukaryotic and prokaryotic cells. On the other hand, the hexosamine biosynthetic pathway (HBP) converts glucose to intermediate products like UDP-N-acetylglucosamine, which is critical for post-translational modifications of proteins, such as protein glycosylation. These 2 pathways are well known to contribute to glucose metabolism, but recent studies indicate modulation of these pathways can alter immune system function. In this review article, the authors present results suggesting how cellular metabolism, including glycolysis and the HBP, occurs in immune cells, and the immunologic significances of such activities. In addition, they provide a review of the literature on the effects of glycolysis and the HBP on various autoimmune, immunologic, and allergic diseases. Finally, the authors briefly introduce the results of their research on the immunologic effects of HBP supplementation (glucosamine) in animal models of allergic disease.

Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

Lower Airway Inflammation in Eosinophilic Chronic Rhinosinusitis as Determined by Exhaled Nitric Oxide

Background: Chronic rhinosinusitis (CRS) is classified into eosinophilic CRS (ECRS) and non-ECRS. The objectives of this study were to evaluate lower airway inflammation by measuring the fractional concentration of exhaled nitric oxide (FeNO) and to examine the effects of endoscopic sinus surgery (ESS) on FeNO in patients with ECRS compared to non-ECRS. Methods: CRS patients with nasal polyps (23 with ECRS and 22 with non-ECRS) were enrolled into this study. ECRS was diagnosed based on the definition proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group. Several clinical markers including blood eosinophil counts, percent of eosinophils in white blood cells (WBC), number of eosinophils in nasal polyps, JESREC scores, total IgE, FeNO, and Lund-Mackay paranasal sinus CT scores were compared between ECRS and non-ECRS. These markers were also tested before and 2 months after ESS. Results: FeNO was significantly higher in patients with ECRS than in non-ECRS patients. When all CRS patients were tested, a significant correlation was found between FeNO and eosinophilic markers including blood eosinophil counts, percent of eosinophils in WBC, number of eosinophils in nasal polyps, and JESREC scores. FeNO showed a significant correlation with Lund-Mackay scores only in ECRS patients. Blood eosinophil counts, percent of eosinophils in WBC, and FeNO decreased after ESS only in ECRS patients. Conclusions: ECRS patients had lower airway inflammation as revealed by an elevated FeNO, which was parallel to the Lund-Mackay CT scores. ESS decreased the blood eosinophils and FeNO, leading to an improvement of the occult pulmonary dysfunction in ECRS patients.

Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses.

Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. Randomised crossover experiment. Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured by UPLC/MS-MS to calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose of DSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations. After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation. Small sample size and short period of drug administration. Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation or HPA axis suppression in healthy horses.

Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide levels for assessing upper airway diseases in asthmatic patients

ABSTRACTBackground: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. Methods: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO50), nasal NO levels, Lund–Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. Results: Asthma was associated with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO50 levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund–Macay (ρ = −0.46, p = 0.03) and ACQ scores (ρ = −0.52, p = 0.009) in asthmatics with CRS. Conclusions: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50 levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

The standardization of inflammation detecting methods in upper and lower airways

Objective:To investigate the standardization of inflammation detecting methods in upper and lower airways. Method:After a five year cooperation with Guangzhou Institute of Respiratory Diseases on inflammatory diseases of airways, we have found a series of evaluation methodology and normative values in upper and lower airways (NO), airway hyper reactivity and cytology (Eos). Result:The normative range of nasal and pulmonary NO is 400-900 ppb and 5-25 ppb respectively. The nasal resistance increased ≥100% and FEV1 fell ≥20% when compared with their respective baselines both illustrating a positive result. The positive value of nasal and pulmonary Eos are ≥2.00/HP and ≥2.5% respectively. Conclusion:The standardization of evaluation methods for upper and lower airway inflammation provides the methodology and research basis for follow-up studies of upper and lower airways.

Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study

BackgroundAllergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).Methods7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.ResultsThere was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.ConclusionsOur data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.

The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis

RationaleIn infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of...

Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection.

Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an asthmatic host and may aid the development of strategies to improve treatments and outcomes for asthmatics harboring influenza virus infection.