Bronchial Mucosa Research Articles

Antitussive, expectorant, and anti-inflammatory effects of Adenophorae Radix powder in ICR mice

Ethnopharmacological relevanceAdenophora triphylla var. japonica is frequently used as an oriental medicinal plant in Korea, China, and Japan for its anti-inflammatory, antitussive, and hepatoprotective effects. Aim of the studyIn the present study, the antitussive, expectorant, and anti-inflammatory effects of AR powder were investigated using animal models to evaluate their potential to treat respiratory disorders. Materials and methodsAR powder was administered orally to mice once daily for 11 days, at dose levels of 400, 200, and 100 mg/kg. Theobromine (TB), ambroxol (AM) and dexamethasone (DEXA) were used as standard drugs for antitussive effects, expectorant effects and anti-inflammatory effects, respectively. Evaluations of antitussive effects were based on changes in body weight, the number of cough responses and the histopathology of the lung and trachea. Expectorant effects were based on changes in the body weight, macroscopic observations of body surface redness, the mucous secretion of the trachea and histopathology of lung (secondary bronchus). Anti-inflammatory effects were based on changes in the body weight, macroscopic observations involving redness and edema of the treated ear, absolute and relative ear weights and histopathology of the treated ears. ResultsAllergic acute inflammation and coughing induced by exposure to NH4OH and symptoms of xylene-induced contact dermatitis were significantly inhibited by treatment with AR powder in a dose-dependent manner. Histological analyses revealed that AR powder decreased the OD values in trachea lavage fluid, reduced body surface redness, thicknesses of intrapulmonary secondary bronchus mucosa, and the number of PAS-positive mucous producing cells. Overall, AR powder administered at 200 mg/kg displayed superior antitussive and expectorant effects as compared to TB (50 mg/kg), and AM (250 mg/kg). At the highest concentration (400 mg/kg) AR powder displayed only moderately improved anti-inflammatory activities as compared to DEXA (1 mg/kg). ConclusionThe results obtained in this study suggest that AR powder exerts dose-dependent, favorable antitussive, expectorant, and anti-inflammatory activities achieved through modulation of the activity of mast cells and respiratory mucous production. Therefore, AR powder may serve as a therapeutic agent in various respiratory disorders, especially those that occur as a result of environmental toxicants.

IgE sensitization in autism children

Introduction Autism Spectrum Disorder (ASD) includes a set of disorders characterized by deficits in communication, social interactions and stereotypical behaviors. Recent studies suggest a higher frequency of atopic diseases (asthma, allergic rhinitis, food allergies...). The aim of our study was to assess IgE sensitization to the most frequent allergens in children with ASD. Methodes The study involved 30 children with ASD and 39 controls. The total IgE as well as the IgE specific to the food (FP2, FP5 and FP51) and respiratory (HP1 and GP1) allergen panels were determined in all children by chemiluminescence technique on the Immulite 2000Xpi. Results There was no significant difference between children with ASD and control in total IgE levels (high IgE level in 66.7% TSA vs 51.3%). Overall analysis of IgE sensitization to common allergens showed a higher frequency in ASD children (65.6% ASD versus 28.9% control, P = 0.002). Also, sensitization to house dust allergens (D1, D2 and I6) and to food allergens of FP5 panel (F1, F2, F4, F13 and F210) was more common in children with ASD (46.87% vs 21.05% and 37.5% vs. 13.16%, respectively, P Discussion Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance. One explanation for such high rates of allergic diseases in the ASD group could relate to immune sensitivity corresponding to intrinsic stress factors and/or psychosocial stress commonly found in children with ASD. In addition, some research has suggested that stress could aid in releasing neurogenic inflammatory agents, which is also identified in bronchial mucosa or immune cells, and conversely, that the immune system could also modulate the central nervous system function via various molecules, including cytokines. Conclusion Our study found an increased IgE sensitization to common respiratory and food allergens in ASD children.

Omalizumab may decrease the thickness of the reticular basement membrane and fibronectin deposit in the bronchial mucosa of severe allergic asthmatics

Introduction: Immunoglobulin E is an important modulator of the inflammatory reaction in allergic asthma. It also contributes to airway remodeling in the course of the disease. The authors evaluated airway structural changes in severe allergic asthma during the omalizumab therapy. Patients and methods: The study included 13 patients with severe allergic asthma treated with omalizumab for at least one year. In each patient clinical, laboratory, and spirometry parameters were evaluated before and after the treatment. In addition, bronchoscopy with bronchial mucosa biopsy and bronchoalveolar lavage was performed. The basal lamina thickness, inflammatory cell infiltration, fibronectin, as well as type I and III collagen accumulation were assessed in bronchial mucosa specimens, together with the assessment of bronchoalveolar lavage cellularity. Results: The omalizumab therapy led to a decrease in the basal lamina thickness (p = 0.002), and to a reduction in fibronectin (p = 0.02), but not collagen deposits in the bronchial mucosa. The decrease in fibronectin accumulation was associated with an improvement in asthma control and quality of life (p = 0.01, both), and a diminished dose of systemic corticosteroids (p = 0.001). It was also associated with a tendency towards reduction of the eosinophil count in the peripheral blood, bronchoalveolar lavage fluid, and bronchial mucosa specimens. Conclusion: Our study has shown that omalizumab, effective in the treatment of severe allergic asthma, may also decrease unfavorable structural airway changes in allergic asthmatics, at least with respect to the fibronectin deposit and an increased thickness of the basal lamina. However, more extensive observational studies are needed to verify the above hypothesis.

Destruction of the bronchial epithelium in patients with severe asthma according to different patterns of inflammation and cold airway hyperresponsiveness.

The aim of the research was to study the state of the bronchial mucosa epi-thelium in relation to the severity of clinical manifestations in severe uncon-trolled asthma depending on the pattern of inflammation and the presence of cold airway hyperresponsiveness. In 48 patients with severe uncontrolled asthma, there were assessed asthma symptoms, clinical signs of cold airway hyperre-sponsiveness, and lung function; the samples of slides were analyzed in the cytological examination of the sputum; the degree of damage to epithelial cells and granulocytes was estimated using the total cell destruction index (CDI). According to the analysis of sputum cytograms, the patients were divided into two groups: group I (22 patients) included persons with eosin-ophilic inflammation pattern (31.0±3.1% of eosinophils and 22.0±2.2% of neutrophils), group II (26 patients) was with mixed inflammation pattern (7.2±1.4 and 71.8±4.2%, respectively). The patients of group II had lower disease control according to Asthma Control Test (ACT; 12.1±0.7 and 17.8±0.2 points, respectively; р<0.05), a greater frequency of exacerbations (4.1±0.3 and 3.2±0.2 per year, respectively; р<0.05), greater incidence of clinical signs of cold airway hyperresponsiveness (79 and 19%, respectively; χ2=14.18; р<0.001); lower lung function (midexpiratory flow rate MEF25-75 was 14.6±1.6 and 20.7±1.9%, respectively; р<0.05); they received a higher dose of the combined medications of inhaled glucocorticosteroid in controller anti-inflammatory therapy (salmeterol/fluticasone at a dose of 705.3±19.7 and 650.7±14.8 µg/day for fluticasone propionate; р<0.05) In patients of group II the correlations of epithelial CDI with neutrophil CDI (r=0.61; p<0.01) and eosinophil CDI (r=0.48; p<0.05), as well as correlation of ACT with neutrophil CDI (r=-0.71; p<0.01) and eosinophil CDI (r=-0.53; p<0.05) were found. The degree of destruction of the epithelium and granulocytes in the inflammatory patterns has diagnostic relevance for the assessment of the severity of the disease, clinical manifestations of the airway response to the cold trigger, and the inertia of achieving control in patients with severe un-controlled asthma.

The distributive and structural characteristics of bronchus-associated lymphoid tissue (BALT) in Bactrian camels (Camelus bactrianus).

BackgroundBronchus-associated lymphoid tissue (BALT), distributed in the bronchial mucosa, plays a critical role in maintaining the mucosal immune homeostasis of the lower respiratory tract. The bronchial tree is a functional structure for gas exchange with the outside environment and maintains basic lung morphology.MethodsTo explore the structural and distributive characteristics of BALT in Bactrian camels, twelve healthy adult Bactrian camels were divided into two groups (six in each group). The lungs, bronchial tree and BALT were observed and analysed systematically through anatomical and histological methods.ResultsThe results showed that Bactrian camel lungs were constituted by the left cranial lobe, left caudal lobe, right cranial lobe, right caudal lobe and accessory lobe, but lacked the middle lobe. The cranial lobe was narrow and small, the caudal lobe was extremely developed (almost four times the cranial lobe in size), and the accessory lobe was smaller than the cranial lobe; the bronchial tree, an unequal dichotomy with a tracheobronchial branch, was composed of dorsal, ventral, lateral and medial bronchiole systems. Isolated lymphoid follicles (the chief type) and aggregates of lymphoid follicles revealed two types of BALT, and germinal centres, follicle-associated epithelium and high endothelial venules could be observed in some well-developed BALT. Additionally, BALT was scattered along the bronchial tree in the entire lung, and the density increased from the trachea to the lower graded branches (densest in the bronchioles) and then decreased, with the occasional location around respiratory bronchioles or among the pulmonary mesenchyme. In the conducting portion, BALT was primarily located in the mucosa lamina propria but was also found in the submucosa, under the muscular layer, and around the submucosal glands and cartilage.ConclusionThe results demonstrated that the lung morphology of Bactrian camels was similar to that of horses, but the bronchial branches were more closely related to those of ruminants. These characteristics were in accordance with the morphological and structural variation regularity of lungs with species evolution. BALT was mainly scattered in the conducting portion, and bronchioles, as the final “checkpoint” in the surveillance, capture and recognition of antigens before pulmonary exchange, were the pivotal locational position of BALT. However, BALT at different depths of the bronchial wall of the conducting portion might be at different developmental stages. Our study provided evidence for further insight into the mucosal immunomodulatory mechanism of BALT in the respiratory system of Bactrian camels.

Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health.

The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.

Additional role of bronchial mucosal biopsy for ciliary structural abnormality in diagnosis of primary ciliary dyskinesia.

Transmission electron microscopy (TEM) is one of diagnostic tests for primary ciliary dyskinesia (PCD). The mucosal samples obtained for cilia examination are generally procured from the nasal turbinate, but these specimens often yield inadequate results. The bronchial mucosa is recognized as an alternative sample, but no study has examined the additional utility of bronchial mucosa compared with nasal mucosa in the diagnosis of PCD. The medical records of 96 patients who underwent TEM for suspected PCD between April 1997 and June 2017 were reviewed. Patients were divided into three groups based on the site of mucosal biopsy: nasal biopsy (NB) group with nasal mucosal biopsy only; bronchial biopsy (BB) group with bronchial mucosal biopsy only; and nasal and bronchial biopsy (NBB) group with a combination of nasal and bronchial mucosal biopsies. The rate of PCD diagnosis was 28.8% (17/59) in the NB group, 41.2% (7/17) in the BB group, and 60.0% (12/20) in the NBB group. The yield of PCD diagnosis significantly increased in the NBB group compared with the NB group (P=0.012). In the NBB group, 25.0% (5/20) of patients were diagnosed with PCD by nasal mucosal biopsy, and 35.0% (7/20) of patients were additionally diagnosed by bronchial mucosal biopsy. The presence of sinusitis or bronchiectasis was not associated with prediction of PCD diagnosis from nasal or bronchial mucosal biopsy. The combination of nasal and bronchial mucosal biopsy for TEM showed higher yields of PCD diagnosis than nasal mucosal biopsy alone.

Retroperitoneal Hydatid Cyst Masquerading as a Retroperitoneal Cystic Tumor

Hydatid disease is an endemic disease, with canines the primary host and humans the intermediate host. Liver, spleen and lungs are most common involved organs, but it can involve any organ. Retroperitoneal hydatid cyst are categorised into two types, primary and secondary. Primary retroperitoneal hydatid cyst is rare disease, with most of the cases diagnosed intra-operatively, hence pre-operative high index of suspicion for any retroperitoneal cystic lesion to prevent inadvertent complication intra-operatively is of utmost important. 25-year male patient presented with right flank pain for 3 months, high grade fever for 10 days. On cross sectional imaging a retroperitoneal cystic lesion of size 7.1×7.6 cm was noted. Leucocytosis was present and rest of the blood parameters were with in normal limits. Patient was planned for surgery with a diagnosis of the retroperitoneal cystic tumour with possible tumour degeneration. On exploration 8×8 cm pelvic retroperitoneal hydatid with daughter cysts and purulent material noted. Diagnosis of infected retroperitoneal hydatid cyst was made and cyst de-roofing and drainage was done. Final diagnosis of hydatid cyst was confirmed by histopathology report. The retroperitoneal hydatid cyst is a rare entity even in endemic areas. First reported in 1958 by Lockhart and Sapinza, an isolated retroperitoneal hydatid cyst could be caused by haematogenous dissemination of protoscoleces after bypassing the liver (veno-venous shunts within the liver and in the space of Retzius) and the lungs or by the gastrointestinal tract into the lymphatic system. Dew and Waddle had favoured airborne transmission and direct implantation of the embryo in the bronchial mucosa as another possible mode of entry. This raises the possibility of an embryo of the parasite entering a venule after penetrating the bronchial mucosa and reaching the left side of the heart to involve other sites and thus bypassing the lung. Spontaneous, traumatic, or surgical rupture of a hepatic cyst may also give rise to cysts in retroperitoneum. The definitive diagnosis of a retroperitoneal hydatid cyst requires a combined assessment of clinical, radiological and serological analysis. Definitive treatment is total cystopericystectomy. Though retoperitoneal hydatid cyst are rare, diagnosis should be considered if any retroperitoneal cyst lesion is noted to prevent the complications of the cyst rupture. The gold standard treatment is total cystopericystectomy. If complete resection is not possible, cyst de-roofing, drainage and adjuvant anti-helminthic should be considered.

Carcinogenic and genotoxic risks of combined exposure to dust and radiation in oxidative stress environment

Rats subjected to coal dust combined with radiation dose of 6 Gy in long-term period demonstrated cytogenetic disorders and changes in bronchial mucosa, arterial and arterioli walls in lung stroma, destructive changes in liver parenchyma with colliquation necrosis foci in liver lobules, on oxidative stress background. Findings are that combined experimental exposure to dust and radiation on oxidative stress background increases carcinogenic and genotoxic risks in animals.

The impact the atmospheric air dust fractions and toxic metals on external respiratory function among chronic obstructive pulmonary disease patients

The study is dedicated to the potential risk determination of external respiratory function (ERF) disorders among chronic obstructive pulmonary disease (COPD) patients under dust fractions and toxic metals influence in Vladivostok atmosphere. The risk assessment included the environmental ERF trigger factors identification among COPD patients by regression analysis, the number of patients responding to factor exposure determination and the analysis of the possible ERF disorders individual risk among COPD patients. It is found that Vladivostok air pollution by dust aerosols and toxic metals directly affects COPD patients’ ERF. The most significant effect on the bronchial mucosa, aggravating bronchial patency (r=11.6%) and lung hyperinflation (r=10.7%) have ultrafine suspended particulate matter (SPM) fractions (0-1 μm). Fine SPM fractions (1-10 μm) affect ERF parameters characterizing bronchial patency only and less than ultrafine fractions (r=10.2%). Toxic metals (Ni, Zn) equally influence bronchial patency and lung tissue hyperinflation indicators among COPD patients (r=29.8% and r=29.1% respectively).

An Outbreak of Fatal Bordetella bronchiseptica Bronchopneumonia in Puppies

Twenty-two newborn puppies that did not receive colostrum exhibited acute respiratory signs and died at a breeding facility. Pathological examinations were performed on four of the puppies. At necropsy examination, the lungs were firm and mottled dark red, consistent with acute bronchopneumonia. Histopathologically, there was marked infiltration of neutrophils and macrophages into the bronchi and alveoli, and gram-negative coccobacilli were attached diffusely to the cilia of bronchial mucosa. Immunohistochemistry for Bordetella bronchiseptica antigen revealed positive labelling of the bacterial agents. On electron microscopy, a large number of coccobacilli were observed attaching to the cilia of bronchial epithelial cells. Real-time polymerase chain reaction amplified a B. bronchiseptica gene from the affected lung tissue. Based on these findings, the four puppies were diagnosed with fatal B. bronchiseptica bronchopneumonia.

Ways of enhancement of the surgical treatment efficacy in treatment of patients, suffering pulmonary tumors

Objective. Efficacy of endoscopic bronchosanation for prophylaxis of preoperative and postoperative complications in patients with pulmonary tumors.
 Маterials and methods. There was studied the efficacy of endoscopic photodynamic therapy in accordance to procedure, elaborated by the authors, including injection of the water solution of a methylene blue dye in concentration 0.04% into tracheobronchial tree, irradiated by laser with the wave length 0.63 mcm, independently and in conjunction with a standard anti-inflammatory therapy as preoperative preparation of tracheobronchial tree in patients, suffering pulmonary cancer. In the investigation 181 patients were included, suffering pulmonary cancer Stages II-III, morphologically confirmed, and with coexistent endobronchitis.
 Results. In accordance to analysis of the pathogenic microflora titer and character in lumen of bronchial tree after preoperative preparation there was established, that while application of independent endoscopic bronchosanation in 55 (87%) observations the pathogenic microflora was absent. While combination of photodynamical bronchosanation in accordance to standard therapy a pathogenic microflora was not revealed in 52 patients. While conduction of a standard preparation without application of a laser therapy microflora was not revealed only in 44.8% observations. Together with the bronchial mucosa metaplasia in some investigated patients the dysplastic changes of bronchial epithelium of various severity degree were registered. Independent endoscopic bronchosanation have leaded to trustworthy lowering of a general rate of the bronchial epithelial dysplasia in the patients tо 36.1%, together with standard anti-inflammatory therapy - tо 42.4%.
 Conclusion. Application of endoscopic photodynamic bronchosanation in accordance to the proposed procedure in preoperative period in the patients with objective to correct a concomitant endobronchitis, as independent option or together with standard anti-inflammatory therapy, leads to reduction of the endobronchial complications rate after operative treatment for pulmonary cancer, comparing with a control group. Еndoscopic bronchosanation is accompanied by significant lowering of severity of endoscopic signs of coexistent endobronchitits and improvement of mucociliary transport. In accordance to microbiological tests in 87 - 88% of patients a complete sanation of bronchial tree and elimination of main histological criteria of inflammation were noted, while in 67.2 - 100% patients – restoration of normal structure of the bronchial tree mucosa.

The influence of basic treatment with tiotropium bromide of patients with chronic obstructive pulmonary disease stage II on the morpho-functional state of bronchial mucosa and the level of type IV collagen in bronchoalveolar lavage fluid.

The objective of the research was to evaluate the influence of basic treatment of patients with chronic obstructive pulmonary disease with tiotropium bromide on the processes of morphological rearrangement and local barrier defence mechanisms in the bronchial mucosa.
 Stage II chronic obstructive pulmonary disease is associated with the damage to the bronchi with proliferation of the connective tissue in its proper plate, clear identification of the basal membrane alteration, the presence of fibroblasts, the activation of fibroblasts/myofibroblasts and mucous glands, which is accompanied by the significant increase of type ІV collagen levels by 6.19 times (p<0.05) in bronchoalveolar lavage fluid as compared to the control group indices.
 The elimination of stage II chronic obstructive pulmonary disease exacerbation and the use of tiotropium bromide within a month was accompanied only by partial improvement of morpho-functional state in relation to both cells of bronchial epithelial lining and adjacent connective tissue of mucosal plate. The prolongation of tiotropium bromide administration from 2 to 6 months, provided positive dynamics of structural morphological changes of the bronchial mucosa (the restoration of the ciliary apparatus of epithelial cells, the normalization of the secretory function of goblet cells, the inactivation of fibroblasts, the initial degeneration of myofibroblasts), thus leading to complete absence of morphological signs of edema or epithelial cell dystrophy.
 Conclusions. In patients with stage II chronic obstructive pulmonary disease, complete absence of morphological signs of edema or dystrophy of epithelial cells, against the background of collagenolysis in the connective tissue of the proper mucous plate of the bronchi and the highest possible decrease in the number of myofibroblasts, with near-complete levels of type IV collagen normalization in the bronchoalveolar lavage fluid, were identified only within a 6-month treatment with tiotropium bromide.

Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy.

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prolonged follow-up are warranted.

STAT6 variants and non-atopic asthma in Pakistani population

Asthma a chronic airway inflammatory disease mainly characterized by airways obstruction. Airway hyper responsiveness particularly in eosinophils and inflammatory mediators affect the bronchial mucosa. Genetic association studies show the association of single nucleotide polymorphisms (SNPs) in the STAT6 gene with asthma risk. Role of Signal transducer and activator of transcription 6 (STAT6) is acute for T-helper 2 (Th2) mediated responses during allergic airway diseases. Objective was to investigate whether the two single nucleotide polymorphism (rs4559 and rs324011) in STAT6 gene are associated with non-atopic asthma risk in Pakistani population. One hundred (100) asthma patients with a positive family history with at least one-first degree asthma affected relative were enrolled. Normal healthy individuals (n=100) were also included as control subjects in the current study. STAT6 SNPs rs4559 and rs324011 were genotyped using SNaPSHOT mini-sequencing assay and the obtained data was statistically analyzed by online SHEsis software. A case-control study for association of STAT6 polymorphisms rs4559 and rs324011 with asthma risk was performed. The SNP rs4559 was found statistically significantly associated with increased susceptibility of developing non-atopic asthma in Pakistani individuals. The SNP rs324011 polymorphism in intron 2 of STAT6 gene may be associated with increased susceptibility of the development of non-atopic asthma as a strong statistically significant difference in allele frequency and genotype was observed between asthmatics and controls showing association with non-atopic asthma in Pakistani individuals. rs4559 and rs324011SNPs in STAT6 found associated with non-atopic asthma risk. We observed the statistically significant association between STAT6 polymorphisms with intrinsic (non-atopic) asthma in Pakistani population.

Effect of acupuncture on TGF-β1/Smads pathway in mice with airway remodeling mic

To investigate the effect of acupuncture on TGF-β1/Smads signaling pathway in the lung tissue of mice with airway remodeling. Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (n=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-β1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- β1 inhibitor (LY2157299), and the relative expressions of type-Ⅰ and Smads proteins were detected using Western blotting. The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-β1 level was significantly elevated in asthmatic mice (P < 0.05); TGF-β1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group (P < 0.05). In the model group, the expressions of α-SMA, TGF-β1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both P < 0.05). In cultured airway smooth muscle cells, the expressions of type-Ⅰ and Smads were significantly higher in cells treated with LY2157299 than in the control cells (P>0.05). Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-β1 and down-regulating the expression of Smads and α-SMA to reduce airway inflammatory response. Airway expressions of type-Ⅰ and Smads proteins remain high after inhibiting TGF-β1. Acupuncture may control asthma progression through the TGF-β1/Smads pathway.

Isolated aggregates of lymphoid cells in the inner bronchial wall in asthma patients.

Here, we report findings in volunteers with bronchial asthma. Biopsies were obtained from the inner bronchial wall before and a short time again after segmental allergen provocation. In most of the baseline biopsies and in all evaluable biopsies after segmental allergen provocation, the follicular lymphoid tissue was detected by immunohistochemistry in the epithelium of these asthmatic patients. The basic occurrence of the tertiary lymphoid tissue in the bronchial mucosa of mild asthmatics was unexpected and may have consequences for the interpretation of pathophysiology, e.g., as a cause or consequence of bronchial asthma.

MAGNESIUM OXIDE PILL ASPIRATION: CASE REPORT

SESSION TITLE: Medical Student/Resident Procedures SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Pill aspiration is uncommon in adults, comprising 2.8% of foreign body aspirations. Symptoms and signs are nonspecific and chest x-rays can be normal in 25% of cases. It can cause airway obstruction, inflammation and stenosis leaving long-term sequelae. Having a high suspicion and doing bronchoscopy early is important in avoiding any long-term sequelae. Here we report a challenging case of bronchus obstruction by magnesium oxide pill aspiration. CASE PRESENTATION: A 60-year-old female presented to the emergency department (ED) at an outside hospital with irritation and cough after choking on a magnesium pill. Chest x-ray did not show any abnormalities so patient was discharged home with instructions to follow up with her primary care physician (PCP). Over the next 2-3 days, she had low-grade fever, coughing fits which brought up bits of the tablet and shortness of breath. She saw her PCP the next day and was given azithromycin. That night, she had a fever of 38.8C and came in to our ED. Vital signs were stable except for oxygen saturation of 91% on room air. She had decreased breath sounds on right mid-to-lower lung field. The remainder of her exam was unremarkable. Chest x-ray showed right middle lobe infiltrates. CT chest revealed a 9x9mm radio-opaque density in the right bronchus intermedius, scattered areas of ground glass opacities and atelectasis in the right middle lobe. She underwent flexible bronchoscopy that showed a white ball-like foreign body near-obstructing the right bronchus intermedius. Mucosa was edematous with mild inflammation, no necrosis or stenosis was noted. The foreign body was successfully removed with grasping forceps in a few smaller pieces (biggest 9 x 7 mm). They were hard, white and chalky, consistent with the magnesium oxide pill. The next day, she reported improvement in her cough and shortness of breath. Her oxygen saturation had improved to 96% on room air and she was discharged home in stable condition. DISCUSSION: Adult patients can present with a clear history of the aspiration event. Symptoms and signs are nonspecific and chest x-rays can be normal in 25% of cases, making the diagnosis challenging. Our patient felt the choking sensation and sought medical attention. Despite her history and due to normal chest x-ray and nonspecific symptoms of cough and normal vital signs, she was initially discharged home without further investigation. In the cases where patients remember a specific aspiration event, despite nonspecific symptoms and normal chest x-ray, further investigation with CT imaging or bronchoscopy should be sought. Left untreated it is possible that there may be further damage to the bronchus through inflammation. CONCLUSIONS: There has been no documentation of the effects of magnesium oxide pill aspiration on the bronchial mucosa. Early bronchoscopy with intervention to remove the pill is important in avoiding any long-term complications. Reference #1: Singh I, Dm S, Dm SD, Ram B. Foreign Body Inhalation in the Adult Population : Experience of 25 , 998 Bronchoscopies and Systematic Review of the Literature. 2015:1438-1448. https://doi.org/10.4187/respcare.03976. Reference #2: Kupeli E, Khemasuwan D, Tunsupon P, Mehta AC. “ Pills ” and the Air Passages, A Continuum. Chest. 2015;147(1):242-250. https://doi.org/10.1378/chest.14-0531. Reference #3: Kinsey CM, Folch E, Majid A, Channick CL. Evaluation and Management of Pill Aspiration. CHEST. 2013;143(6):1791-1795. https://doi.org/10.1378/chest.12-1571. DISCLOSURES: no disclosure on file for Ji Hyun Rhee; No relevant relationships by Jack Tomen, source=Web Response

TRACHEOBRONCHIAL FOREIGN BODY ASPIRATION: THE GREAT MIMICKER

SESSION TITLE: Signs and Symptoms of Chest Disease SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Tracheobronchial foreign body (FB) aspiration is rare but it can mimic other, more common conditions. CASE PRESENTATION: A 53 y/o male with COPD presented with a chronic cough. The cough was non-productive and intermittent with no identifiable triggers. He was treated for bronchitis several times with no real improvement. He denied hemoptysis, night sweats or weight loss. CXR showed a right middle lobe infiltrate with volume loss. Chest CT revealed a large area of bronchiectasis and interstitial infiltrate in the medial right lower lung field, right hilar lymphadenopathy and a right hilar nodule measuring 2cm x2.3cm transversely, thought to represent a central malignancy. He had a 20 pack year smoking history. Physical exam was unremarkable for pulmonary abnormalities. Bronchoscopy revealed an erythematous, fungating, polypoid lesion at the orifice of the RML. What appeared to be a foreign body was seen amidst the irritated bronchial mucosa. This foreign body was removed with forceps and was later identified as a drinking straw. The surrounding bronchial mucosa was edematous and erythematous. The distal RML contained thick secretions which were suctioned and cultured. Endobronchial biopsies were performed at the area of the FB removal to ensure no malignant changes were present. The patient continued to do well post-procedure and his cough eventually resolved. DISCUSSION: Tracheobronchial FB aspiration is uncommon and only accounts for about 0.16 to 0.33% of adult bronchoscopic procedures.1 A choking episode followed by coughing and dyspnea are often described, but not always. The retained FB can then cause symptoms that mimic chronic conditions such as COPD, recurrent pneumonia1 and possible malignancy. Most episodes are seen in children, but up to 25% of cases involve adults,1 making the differential quite broad if there is a lack of acute symptoms. In adults, neurological deficits, altered mental status, impaired cough reflex and intoxication increase the risk of FB aspiration.1,2 If asymptomatic, FBs are often found incidentally on imaging. CXR will only identify FBs about 25% of the time, therefore chest CT is preferred.1 Chest CT often shows focal abnormalities such as: atelectasis, bronchiectasis, consolidation1 or findings suggestive of malignancy. Bronchoscopy with removal of the FB should be completed early after identification to prevent further lung damage. Traditionally, rigid bronchoscopy was performed, but flexible bronchoscopy is becoming more frequently used.1 CONCLUSIONS: Tracheobronchial FB aspiration is uncommon and can present as more common chronic conditions or even suggest malignancy. Our patient had a chronic cough and CT findings suggestive of malignancy. Upon bronchoscopy, the abnormality was identified as a previously aspirated FB that had likely been in place for months to years. This case illustrates a FB aspiration presenting as possible malignancy. Reference #1: Hewlett JC, Rickman OB, Lentz RJ, Prakash UB, Maldonado F. “Foreign body aspiration in adult airways: therapeutic approach.” Journal of Thoracic Disease. 2017;9(9):3398-3409. https://doi.org/10.21037/jtd.2017.06.137. Reference #2: Alharthi BJ, et al. “Occult Foreign Body in the Lung Mimicking Bronchogenic Carcinoma.” Case Reports, 2014; https://doi.org/10.1136/bcr-2014-207438. DISCLOSURES: No relevant relationships by Raed Alalawi, source=Web Response No relevant relationships by Audra Schwalk, source=Web Response

Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa.

The efficacy of the adaptive humoral immune response likely requires diverse, yet focused regional B cell antibody production throughout the body. Here we address, in the first study of its kind, the B cell repertoire in the bronchial mucosa, an important barrier to antigens inhaled from the atmosphere. To accomplish this, we have applied high-throughput Adaptive Immune Receptor Repertoire Sequencing (AIRR-Seq) to 10 bronchial biopsies from altogether four different sites in the right lungs from an asthmatic patient and a healthy subject. While the majority of identified B cell clones were restricted to a single site, many were disseminated in multiple sites. Members of a clone were shared more between adjacent biopsies than between distal biopsies, suggesting local mucosal migration and/or a homing mechanism for B cells through the blood or lymph. A smaller fraction of clones spanned the bronchial mucosa and peripheral blood, suggesting ongoing trafficking between these compartments. The bronchial mucosal B cell repertoire in the asthmatic patient was geographically more variable but less diverse compared to that of the healthy subject, suggesting an ongoing, antigen-driven humoral immune response in atopic asthma. Whether this is a feature of atopy or disease status remains to be clarified in future studies. We observed a subset of highly mutated and antigen-selected IgD-only cells in the bronchial mucosa. These cells were found in relative high abundance in the asthmatic individual but also, albeit at lower abundance, in the healthy subject. This novel finding merits further exploration using a larger cohort of subjects.