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Inhalation exposure to cigarette smoke and e-cigarette aerosol is known to alter the respiratory immune system, particularly cytokine signaling. In assessments of health impacts of tobacco product use, cytokines are often measured using a variety of sample types, from serum to airway mucosa. However, it is currently unclear whether and how well cytokine levels from different sample types and the airway locations they represent are correlated, making comparing studies that utilize differing sample types challenging. To address this challenge, we compared baseline cytokine signatures in upper and lower airways and systemic samples and evaluated how groups of coexpressed cytokines change with tobacco product use. Matched nasal lavage fluid (NLF), nasal epithelial lining fluid (NELF), sputum, and circulating serum samples were collected from 14 nonsmokers, 13 cigarette smokers, and 17 e-cigarette users and analyzed for levels of 22 cytokines. Individual cytokine signatures were first compared across each sample type, followed by identification of cytokine clusters within each sample type. Identified clusters were then evaluated for potential alterations following tobacco product use using eigenvector analyses. Individual cytokine signatures in the respiratory tract were significantly correlated (NLF, NELF, and sputum) compared with randomly permutated signatures, whereas serum was not significantly different from random permutations. Cytokine clusters that were similar across airway sample types were modified by tobacco product use, particularly e-cigarettes, indicating a degree of uniformity in terms of how cytokine host defense and immune cell recruitment responses cooperate in the upper and lower airways. Overall, cluster-based analyses were found to be especially useful in small cohort assessments, providing higher sensitivity than individual signatures to detect biologically meaningful differences between tobacco use groups. This novel cluster analysis approach revealed that eigencytokine patterns in noninvasive upper airway samples simulate cytokine patterns in lower airways. [ABSTRACT FROM AUTHOR]

Introduction: The effect of nitric oxide (NO) on the human body is very important due its physiological regulation of the following functions of airways: modulation of ciliary movement and maintenance of sterility in sinuses. Aim: To evaluate the diagnostic significance of NO concentrations in exhaled air from the upper and lower airways in patients diagnosed with allergic rhinitis (AR). Material and methods: The subjects included in the study were a group of 30 people diagnosed with sensitivity to environmental allergens and a control group consisting of 30 healthy subjects. The measurement of NO in the air exhaled from the lower and upper airways was performed using an on-line method by means of Restricted Exhaled Breath (REB), as well as using the measurement procedure (chemiluminescence) set out in the guidelines prepared in 2005 by the American Thoracic Society and the European Respiratory Society. Results: In the late phase of the allergic reaction, higher values of the level of exhaled NO concentration from the lower airways were observed in the groups of subjects up to the threshold values of 25.17 ppb in the group of subjects with year-round allergic rhinitis and 21.78 ppb in the group with diagnosed seasonal allergic rhinitis. The difference in the concentration of NO exhaled from the lungs between the test group and the control group in the 4th h of the test was statistically significant (p = 0.045). Conclusions: Exhaled NO should be considered as a marker of airway inflammation. It plays an important role in the differential diagnosis of allergy. [ABSTRACT FROM AUTHOR]

Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf ® and Alveofact ® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a common human pathogen, which is regularly part of the normal microflora found in the nose and skin. It represents a significant threat to human health, not in the least because of its capability to produce exotoxins, which have superantigenic properties. These exotoxins, in particular the staphylococcal enterotoxins (SEs), are known to be involved in the modulation and aggravation of airway inflammation. Indeed, recent studies show an important impact of SEs on the natural course of allergic rhinitis, nasal polyposis, asthma and COPD. This review outlines the current knowledge on the influence of SEs on airway inflammation. We highlight, in particular, the recent evidence on their role in asthma. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: A comprehensive proteomic profiling of nasal epithelium (NE) is described. This study relies on simple subcellular fractionation used to obtain soluble- and membrane-enriched fractions followed by 2-dimensional liquid chromatography (2D-LC) separation and tandem mass spectrometry (MS/MS). The cells were collected using a brushing technique applied on NE of clinically evaluated volunteers. Subsequently, the soluble- and the membrane-protein enriched fractions were prepared and analyzed in parallel using 2D-LC-MS/MS. In a set of 1482 identified proteins, 947 (63.9%) proteins were found to be associated to membrane fraction. Grand average hydropathy value index (GRAVY) analysis, the transmembrane protein mapping and annotations of primary location deposited in the Human Protein Reference Database (HPRD) confirmed an enrichment of hydrophobic proteins on this dataset. Ingenuity Pathway Analysis (IPA) of soluble fraction revealed an enrichment of molecular and cellular functions associated with cell death, protein folding and drug metabolism while in membrane fraction showed an enrichment of functions associated with molecular transport, protein trafficking and cell-to-cell signaling and interaction. The IPA showed similar enrichment of functions associated with cellular growth and proliferation in both soluble and membrane subproteomes. This finding was in agreement with protein content analysis using exponentially modified protein abundance index (emPAI). A comparison of our data with previously published studies focusing on respiratory tract epithelium revealed similarities related to identification of proteins associated with physical barrier function and immunological defence. In summary, we extended the NE molecular profile by identifying and characterizing proteins associated to pivotal functions of a respiratory epithelium, including the control of fluid volume and ionic composition at the airways'' surface, physical barrier maintenance, detoxification and immunological defence. The extent of similarities supports the applicability of a less invasive analysis of NE to assess prognosis and treatment response of lung diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. [Copyright &y& Elsevier]

Background: Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. Objective: To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. Methods: DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. Results and Conclusions: DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Background: Upper and lower airways allergic disease is currently considered unitarily. Allergic inflammation in one site can extend to other sites of the respiratory tract. Objective: To evaluate bronchial inflammation before and after allergen-specific nasal challenge (ASNC) in rhinitic and asthmatic children, considering the different levels of allergen exposure, i.e. summer (low) and winter (high). Methods: Fourteen children with rhinitis and 15 with rhinitis and asthma, all monosensitized to mites and 10 healthy controls were studied. Nasal IgE were measured before ASNC in summer and in winter season. Nasal clinical score, eosinophil cationic protein (ECP), nasal tryptase, bronchial clinical score, FEV1, PEF, sputum ECP, sputum tryptase and exhaled nitric oxide (eNO) were evaluated before and after ASNC in summer and winter season. Results: Nasal scores significantly increased after ASNC in rhinitic and asthmatic children in both seasons. Nasal IgE were significantly higher in summer compared to winter. Bronchial symptoms, FEV1 and PEF showed no mean differences in rhinitic and asthmatic children after ASNC, with an increase of bronchial symptoms and a decrease of FEV1 and PEF occurring in 3/15 asthmatic children. In both groups nasal tryptase and ECP after ASNC significantly increased in summer and winter, while sputum tryptase was undetectable before or after ASNC in both groups. Sputum ECP and eNO at baseline were significantly higher in patients than in controls (summer , winter ). Sputum ECP significantly increased after ASNC in 3/15 asthmatics in summer and in 11/15 in winter, as well as in 3/14 rhinitics in summer and in 4/14 in winter. eNO significantly increased after ASNC in 3/15 asthmatics in summer and in 10/15 in winter, and in 1/14 rhinitics in summer and in 4/14 in winter. A significant median increase of sputum ECP () and eNO () after ASNC in asthmatic and of eNO () in rhinitic children was also found in winter. Conclusions: Basal sputum ECP and eNO values, significantly higher before ASNC in rhinitic patients compared to control subjects, confirm the inflammatory link of upper and lower airways. The more frequent detection of inflammatory changes induced by ASNC in winter suggests that allergen exposure favours the transfer of nasal inflammation to lower airways. [Copyright &y& Elsevier]

Objective: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease., Methods: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated., Results: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1 st second (FEV 1 ) significantly improved after surgery from 3.23 to 3.45 L/s., Conclusions: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases., (Copyright © 2021 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

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., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

In spite of the amount of literature demonstrating the relationship between upper and lower airways, both from the anatomical, and pathophysiological point of view, little is known about the epidemiology, diagnosis and treatment of the Rhino-Bronchial Syndrome (RBS). After the publication, in 2003, of a Consensus Report defining the Rhino-Bronchial Syndrome, an interdisciplinary group of experts made up from the Italian ENT Society (SIO) and the Interdisciplinary Scientific Association for the Study of Respiratory Diseases (AIMAR) met again in 2005 in order to study a protocol which would have, as the main tasks, the analysis of RBS signs and symptoms and standardization of the diagnostic approach. A secondary endpoint was to characterize the most effective therapeutic options and to correct the great dyshomogeneity in the therapeutic approaches. With this aim, 9 ENT and Pneumology Centres were selected, based on the ability to multidisciplinary cooperation, availability of useful instrumentation and homogeneous distribution over the entire National territory. Overall, 159 patients were enrolled according to clinical history (major and minor symptoms of upper and lower airways) and inclusion/exclusion criteria. All underwent a two level diagnostic approach. In 116 patients, the diagnosis was confirmed on the basis of I level (rhinopharyngeal endoscopy and basal spirometry, respectively, for upper and lower airways) examination. Allergic and infectious diseases were significantly more frequent (37.9% vs 20.9% and 73.3% vs 46.55, respectively) in patients with a confirmed diagnosis for Rhino-Bronchial Syndrome. Nasal obstruction (93%), rhinorrhoea (75%), cough (96%) and dyspnoea (69%) were the more frequent symptoms. The presence of meatal secretions or polyps were the clinical findings significantly differing at endoscopy in the two groups. After 3 months of treatment, according to "good clinical practice" (inhaled steroids, antibiotics, nasal lavages), 96% of the patients recovered. On the basis of these results, a diagnostic flow-chart is proposed according to which the persistence of some symptoms (cough, dyspnoea, rhinorrhoea and nasal obstruction) should lead the patient to a multidisciplinary and multi-level diagnostic approach by an otorhinolaryngology and a pneumology specialist working together for a definitive diagnosis. The recovery rate of about 94% of patients after 3 months of treatment, stresses the importance of a correct diagnosis.