Intermittent Wheezing Research Articles

Bridging Bronchus – An Unsuspected Airway Anomaly Associated with Congenital Heart Disease: A Case Report with Review of Literature

Abstract Background: The association of airway anomalies with congenital heart disease (CHD) is common, but often remains undetected, due to a lack of awareness. We describe the unfortunate demise of an infant with CHD due to delayed diagnosis of a bridging bronchus (BB) with multifocal bronchial stenosis. Clinical Description: An 18-month-old boy, who was a known case of ventricular septal defect (VSD), was hospitalized for the third time with symptoms of pneumonia and congestive heart failure. He also had intermittent stridor and wheeze similar to his earlier illnesses. Management and Outcome: After stabilization with bubble continuous positive airway pressure, antibiotics, and diuretics, he underwent surgery for the VSD and got extubated successfully on day 3. Subsequently, however, he failed to get weaned off further from respiratory support and started having recurrent episodes of stridor along with suprasternal retractions and wheeze. Computerized tomography (CT) showed BB with multifocal stenosis of the airway and sequestration of the left lower lobe of the lung. He developed pneumonia and succumbed to the illness before he could be considered for surgical correction of the airway anomalies. Conclusion: Awareness about associated airway anomalies and their preoperative detection may alter prognostication, parental counseling, surgical approach, and final outcome.

INTERMITTENT OBSTRUCTION: A CASE OF ENCAPSULATED ENDOBRONCHIAL HAMARTOMA EXHIBITING A CUP-IN-BALL EFFECT

INTERMITTENT OBSTRUCTION: A CASE OF ENCAPSULATED ENDOBRONCHIAL HAMARTOMA EXHIBITING A CUP-IN-BALL EFFECT

Tracheal resection and anastomosis in a dog with an osteochondroma

AbstractA 2‐month‐old golden retriever was presented with a history of intermittent wheezing and inspiratory stridor. Previous thoracic radiographs revealed the presence of a discrete opacity partially obscuring the trachea at the level of the thoracic inlet. Through tracheoscopy, a smooth, broad‐based intratracheal mass was visualised just past the thoracic inlet that made up about 80% of the tracheal diameter. Histological examination of biopsies obtained during this procedure was consistent with tracheal osteochondroma. The mass was removed by resection and anastomosis of the trachea through a cervical approach. Histopathology of the excised mass confirmed the prior diagnosis of osteochondroma. Re‐evaluation and repeat thoracic radiographs 6 months postoperatively showed complete resolution of clinical signs and no evidence of recurrent disease. This case demonstrates that tracheal resection and anastomosis can be a viable and curative surgical procedure for some masses, including osteochondromas, within the trachea.

Cost Utility of Intermittent Inhaled Corticosteroids in Preschoolers with Viral-Triggered Wheeze.

Background: Evidence has demonstrated that adding intermittent inhaled corticosteroids (ICS) to treatment with short-acting b2-agonists (SABAs) in children 5 years of age and younger who experience intermittent viral-induced wheezing (VIW) reduces the risk of severe exacerbations. However, there is concern about whether the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of intermittent ICS in children 5 years of age and younger who experience intermittent VIW. Methods: We constructed a probabilistic Markov model to estimate the cost and quality-adjusted life-years (QALYs) of intermittent ICS compared with SABA reliever therapy in preschoolers with viral-triggered wheezing in Colombia. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $5,180. Results: In an analysis of the Markov cohort model, we estimated a gain of 0.2 QALYs per patient per year on intermittent ICS compared with SABA and a reduction of cost per patient of USD $37 per year. This position of dominance negated the need to calculate an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses, our base case results were robust to variations of all assumptions and parameters. Conclusion: Adding intermittent ICS to treatment with SABAs in children 5 years of age and younger who experience intermittent VIW was found to be cost effective. These results could improve the use of health care resources, especially in settings with limited economic resources.

Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates.

Rationale: Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. Objectives: We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence/absence of wheezing. Methods: We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence/recurrence). We applied partition-around-medoids clustering on these variables to derive phenotypes in five birth cohorts. We investigated within- and between-phenotype differences compared with binary latent class analysis models and ascertained associations of these phenotypes with asthma and lung function and with polymorphisms in asthma loci 17q12-21 and CDHR3 (cadherin-related family member 3). Measurements and Main Results: Analysis among 7,719 participants with complete data identified five spell-based wheeze phenotypes with a high degree of certainty: never (54.1%), early-transient (ETW) (23.7%), late-onset (LOW) (6.9%), persistent (PEW) (8.3%), and a novel phenotype, intermittent wheeze (INT) (6.9%). FEV1/FVC was lower in PEW and INT compared with ETW and LOW and declined from age 8 years to adulthood in INT. 17q12-21 and CDHR3 polymorphisms were associated with higher odds of PEW and INT, but not ETW or LOW. Latent class analysis- and spell-based phenotypes appeared similar, but within-phenotype individual trajectories and phenotype allocation differed substantially. The spell-based approach was much more robust in dealing with missing data, and the derived clusters were more stable and internally homogeneous. Conclusions: Modeling of spell variables identified a novel intermittent wheeze phenotype associated with lung function decline to early adulthood. Using multidimensional spell variables may better capture wheeze development and provide a more robust input for phenotype derivation.

Periostin and IFN-γ levels in serum and nasopharyngeal aspirate in infants with viral-induced wheezing - 2 year follow-up.

The present study assesses the immune response in children with viral-induced wheezing by examining the two factors-interferon-gamma (IFN-γ) and periostin in serum and nasopharyngeal aspirate (NPA). The aim was to find a pattern with the severity and frequency of wheezing episodes. Sixty-nine infants (40 boys and 29 girls), with a mean age of 11.4±6 (2 - 23) months, hospitalized with a first or recurrent episode of bronchial obstruction were enrolled in this study. The serum and NPA concentrations of IFN-γ and periostin were assessed by ELISA methodology. Fifty of the children (72%) were followed for 2 years. We detected lower NPA IFN-γ production in boys, infants with atopic status, family history of asthma, and respiratory syncytial virus infection. Recurrent wheezing in children was associated with a twice lower concentration of IFN-γ in NPA compared to those with the first episode (7.1 vs. 14.8 pg/ml, p=0.05). Higher serum periostin level was established in children over 12 mo in the group of recurrent wheezers with persistent manifestations compared to those without symptoms during the follow-up (410.5 vs. 269.7 ng/ml, p = 0.03). Multivariate logistical regression model assessed high level of serum periostin, male gender, atopy, family history of asthma, and severity of the attack as significant risk factors for persistent compared to intermittent wheezing (r < sup > 2 < /sup > = 0.87, p = 0.04). Our results demonstrated that recurrent viral-induced wheezing is associated with decreased IFN-γ production and increased periostin response and their correlation with severity and persistence of symptoms were the main outcome measures.

ALL THAT PET POSITIVE IS NOT CANCER

TOPIC: Procedures TYPE: Fellow Case Reports INTRODUCTION: PET (Positron emission tomography)/CT (Computed tomography) is a common modality used to diagnose and stage various malignancies. Radiotracer FDG (Fluoro18-deoxyglucose) is not cancer-specific and false-positive results may be observed in a wide variety of non-malignant conditions. Here we describe a patient with FDG avid left lower lobe endobronchial mass. CASE PRESENTATION: 75 years old female with a medical history significant for type 2 diabetes mellitus, seizure disorder was referred to pulmonology clinic with shortness of breath, intermittent wheezing, and non-productive cough for 2 months. She denied chest pain, orthopnea, fever, chills, weight or appetite changes, night sweats. The patient is a former smoker with less than 20 pack-year, quit two decades ago. On physical exam, the patient was saturating 92% in room air. BMI was 44.99 kg/m2. Lung examination showed reduced breath sounds at the left lung base. The rest of the exam was unremarkable. The pulmonary function test was normal. Outpatient evaluations were unremarkable. Chest X-ray showed left lower lobe infiltrates. CT chest showed left lower lobe consolidation vs atelectasis of left lung base followed with PET/CT which revealed increased FDG uptake in left lower lobe intraluminal density with SUV 6.5 concerning for malignancy with endobronchial involvement vs inflammatory process. Diagnostic bronchoscopy showed left lower lobe bronchus with significant mucosal hyperemia and edema with yellowish-white foreign body (FB) which was successfully retrieved with endobronchial biopsy forceps and noted to a piece of corn. The patient's symptoms resolved. DISCUSSION: The reported false positive rate of PET/CT was 13% and attributed to FDG uptake by inflammatory cells at the sites of inflammation or infection. Most common FDG avid non-infectious inflammatory etiologies include sarcoidosis, atherosclerosis, pneumoconiosis, and focal foreign body-related inflammation. FB aspiration in the tracheobronchial tree is rare in adults and usually presents with subtle respiratory symptoms with paucity in imaging. Risk factors include loss of consciousness from trauma, drug, seizure disorder or alcohol intoxication, dysphagia related to age-related slowing, stroke, dementia, or Parkinson's disease. In our case, false positives artifacts were related to a focal foreign body (FB) related inflammation with an elevated risk of aspiration related to a seizure disorder, and advanced age. Removal of FB from the tracheobronchial tree may be achieved with flexible bronchoscopy with biopsy forceps or retrieval basket. Rigid bronchoscopy may be needed if flexible bronchoscopy was unsuccessful. CONCLUSIONS: It is essential to understand false positive results while interpreting PET/CT results. FB aspiration in adults is rare and high clinical suspicion is necessary for the diagnosis. Removal of FB can usually be accomplished with bronchoscopy. REFERENCE #1: Common causes of False-positive F18 FDG PET/CT scans in oncology- Kevin R Carter, Eduard Kotlyarov; Vol,50, special number: pp.29-35, September 2007 Brazilian Archives of Biology and Technology- an International Journal. REFERENCE #2: Non-asphyxiating tracheobronchial foreign bodies in adults- Lan RS, Eur Respir J. 1994;7(3): 510 REFERENCE #3: Tracheobronchial foreign bodies in adults- Limper AH, Prakash UB, Ann Intern Med. 1990; 112(8):604 DISCLOSURES: No relevant relationships by Mansur Assaad, source=Web Response No relevant relationships by Rajamurugan Meenakshisundaram, source=Web Response No relevant relationships by FARAZ Siddiqui, source=Web Response

DOES ASTHMA MANAGEMENT DIFFER BETWEEN INDIGENT AND PRIVATE CLINICS?

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Asthma is a reversible airway obstructive disorder characterized by airway inflammation and bronchoconstriction with symptoms such as intermittent cough, wheeze and shortness of breath. Global Initiative for Asthma (GINA) guidelines are published annually to help in decreasing the morbidity and mortality associated with asthma by guiding management. In this study, we compared management in two different population subsets, patients from the indigent clinic and from the private insured clinic, and determined if there was a disparity in asthma management. METHODS: After approval from the Institutional Review Board, a retrospective chart review was conducted among all patients with the diagnosis of asthma in two Internal Medicine resident-run community clinics from January 2016 to November 2019. Baseline demographics, asthma severity, number of exacerbations requiring hospital visits, and medication management were reviewed. RESULTS: Chart review of 128 patients between the indigent clinic (A), which included 94 patients, and private clinic (B), which included 34 patients, showed that there was no significant difference in management between the two clinics. Table 1, resulted below, shows whether asthma was managed appropriately between the two clinics based on the severity of asthma. If a patient is diagnosed with either cough variant or intermittent asthma, appropriate management would include the use of a SABA or as needed ICS, at minimum, for control of symptoms as per GINA guidelines. For patients diagnosed with persistent asthma, appropriate management included a stepwise approach with maintenance therapy and a rescue inhaler. 70 out of 80 patients (87.5%) at the indigent clinic (A) had appropriate management and 26 out of 33 patients (78.8%) at the private clinic (B) had appropriate management. CONCLUSIONS: Disparities in healthcare do exist but between the two internal medicine resident-run clinics, there was no difference in appropriate management of asthma. CLINICAL IMPLICATIONS: Although there was no difference in management of asthma between the two clinics, education will be needed on proper management since neither clinic had complete adherence to GINA guidelines for management. DISCLOSURES: No relevant relationships by Saiara Choudhury, source=Web Response no disclosure on file for Jack Davitt; No relevant relationships by Reema George, source=Web Response No relevant relationships by Salim Surani, source=Web Response

Severe preschool asthmatics have altered cytokine and anti-viral responses during exacerbation.

Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple-trigger wheeze (MTW). To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes. Multicenter, prospective, observational cohort (VIRASTHMA-2). Children (1-5years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8weeks later (T2), and sputum samples were collected at T1. A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN-γ (P=.002), IL-5 (P=.020), TNF-α (P=.038), IL-10 (P=.002), IFN-β (P=.036), and CXCL10 (P=.006) and lower levels of IFN-γ (P=.047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN-γ (P=.045) and CXCL10 (P=.013). Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro- and anti-inflammatory cytokines, and antiviral responses during severe virus-induced exacerbation.

Severe Oro-laryngeal Thrush Following Excessive Use of Steroid Inhaler

Introduction: Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play an important role in the treatment of bronchial asthma. Its usage facilitates disease control in asthmatic patients, resulting in improved quality of life. Because of its benefit, the inhaled steroid is used extensively, at higher doses and for longer duration. However, the localized effects of inhaled corticosteroids on oral/laryngeal mucosa, such as fungal infections can be problematic. Case Report: We report a case of oropharyngeal and laryngeal candidiasis following a long period and high doses of inhaled steroid in a 42-year-old male. He presented with a complaint of increasing tiredness, phlegm, intermittent wheezing and hoarseness for 2-3 months. There was no weight loss or loss of appetite. He has been using inhaled steroids and long acting bronchodilators in increasing doses for his claimed ‘wheezing’ despite the negative history of asthma. The inhaled steroids were fluticasone dipropionate at doses of 500-100 mcg daily for 2-3 months. Results: Examination revealed widespread oral thrush involving the oral cavity, oropharynx and larynx. There was no cushingoid habitus. His muscle power was of 5/5 bilaterally and his lungs were clear. Lung function and chest film were also normal. The steroid was stopped immediately and flucanozole and nystatin syrup were prescribed. The patient made an uneventful and complete recovery. Conclusion: We conclude that patients on inhaled corticosteroids should be monitored for local side effects. Physicians should be aware not only of the systemic but also of the local side effects of inhaled corticosteroids. Patients may increase doses without the knowledge of their physicians and subsequently suffer the adverse effects either local or systemic.

Emerging Therapies in the Treatment of Early Childhood Wheeze.

Phenotypic variation in asthma, especially early childhood asthma, is increasingly recognized. Although inhaled corticosteroids are recommended as first-line therapy, it has less efficacy in controlling intermittent wheeze due to viral-induced symptoms in early childhood. This article reviews 2 emerging therapies in particular for early childhood wheeze: azithromycin and bacterial lysate therapy. Azithromycin's effects are both antibacterial and anti-inflammatory, and it has been shown in 2 studies in preschoolers to prevent progression to severe respiratory tract infection and decrease duration of wheeze. Bacterial lysates work at multiple stages in the innate and adaptive immune response and have been shown to decrease mean wheeze duration in particular in the preschool age. More research is required although both therapies offer a promising future approach, in particular in the nonatopic preschool wheezer, as we move toward a more personalized approach to childhood asthma.

Primary Pulmonary Adenocarcinoma in a Cow

Background: Primary neoplasms of the respiratory tract are rare in cattle, and they present with nonspecific clinical signs and are usually found at post-mortem. Pulmonary adenocarcinoma of the acinar type is uncommon, and information about this neoplasm in cattle is scarce. This paper aims to describe the clinical, laboratory, and pathological findings in a cow with this neoplasm.Case: A 10-year-old, adult, mixed-breed Holstein cow weighing 300 kg was referred to the Garanhuns Cattle Clinic of the Campus of Federal Rural University of Pernambuco, Brazil, with a history of decreased appetite, tiredness, weight loss, and difficulty in breathing for two months. The animal had been treated at the farm of origin with enrofloxacin, florfenicol, and flunixin meglumine. The animal’s appetite improved, but no improvement in the respiratory symptoms was observed. On examination at our center, the cow was in an orthopedic position, with neck extension and elbow abduction; and it remained in a recumbent position. The cow had neutrophilia, normochromic normocytic anemia, and hyperfibrinogemia. The body condition score (BCS) was 1 (BCS ranges from 1 to 5), and the cow had moderate enophthalmia, serous secretions in nostrils, tachycardia, and tachypnea. It also had increased breathing intensity; increased breath sounds in the cranial regions of both lungs; areas of reduced breath sounds in the medial portions of the lungs; intermittent wheezing in the cranial region of the left lung medially and in the cranial region of the right lung medially; intermittent crepitations in the cranial region of the right lung medially; reduced thoracic expansion; and expiratory dyspnea. Pulmonary ultrasonography revealed hyperechogenic multifocal structures in both lungs. In view of the severe clinical condition and unfavorable prognosis, the owner opted for euthanasia. Necropsy revealed that there was a significant amount of yellow fluid in the thoracic cavity, and the cut surfaces of the lungs were covered with fibrin and pleural adhesions. The lungs had irregular surfaces with multifocal nodules of various sizes and firm consistency. The texture of the cut nodules was solid, and the nodules had a yellowish color. Histologically, the pulmonary nodules were composed of neoplastic cells. They were pleomorphic, infiltrative epithelial cells with little cytoplasm; large and spherical nuclei with abundant euchromatin; occasional anisokaryosis; visible nucleolus; and numerous mitotic figures. Results of anti-cytokeratin immunohistochemistry were strongly positive for cytokeratin in the lungs and lymph nodes. Discussion: The diagnosis of acinar pulmonary adenocarcinoma was based on clinical, laboratory, histopathological, and immunohistochemical findings. Clinical signs and lung ultrasound suggested a severe respiratory disease. Pulmonary tumors are usually solid, and they show areas of central necrosis that resemble granulomas. However, the histopathological findings in the current case were compatible with a primary pulmonary neoplasm. Primary pulmonary neoplasms, although rare, should be considered in the differential diagnosis of weight loss, cachexia, and respiratory symptoms in adult cattle. The morphological pattern and the strong immunoreactivity on immunohistochemical examination were conclusive for a diagnosis of a primary pulmonary adenocarcinoma of the acinar type because these tumors specifically contain cytokeratin.

Adalimumab drug induced pulmonary infiltrates and eosinophilia

Adalimumab (Humira) is a recombinant monoclonal antibody that binds to human tumour necrosis factor alpha (TNF-alpha) and, consequently, interferes with the cytokine-driven inflammatory process. It is used to treat a number of conditions including ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, psoriatic arthritis and rheumatoid arthritis. One of the rare side effects of adalimumab is interstitial lung disease. Our case report is a 61-year-old female who was referred for increasing intermittent wheezing, dyspnea and cough with a many year history of asthma. She had received 3 (monthly) doses of adalimumab for her Crohn’s disease. Imaging revealed patchy densities bilaterally. Her blood count had an elevation of eosinophils. With cessation of the medication the pulmonary infiltrates resolved and her blood eosinophilia returned to normal. Given that the investigations for eosinophilic granulomatosis with polyangiitis (EGPA) and allergic bronchopulmonary aspergillosis (ABPA) were negative this was highly suspicious for an adalimumab drug induced pulmonary infiltrates and eosinophilia. There is a paucity of reports of eosinophilic induced lung disease associated with adalimumab. The pneumotox.org registry has eosinophilic pneumonia listed as a pattern of disease with less than 10 cases reported from a (suspected) drug reaction to adalimumab. This case gives strength to suggestion that adalimumab is an offending drug that may cause pulmonary infiltrates and eosinophilia.

A RARE CASE OF ANTERIOR SEGMENT TB IN AN ELDERLY PATIENT WITH ENDOBRONCHIAL TB

SESSION TITLE: Chest Infections 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Anterior Segment Tuberculosis (ASTB) is an uncommon manifestation of pulmonary tuberculosis (TB). The incidence of localized anterior segment involvement is approximately 2.8%, occurring mostly in children, often associated with primary pulmonary TB. The incidence of ASTB in reactivation TB is low. We describe a case of an elderly patient with reactivation pulmonary TB infection, presenting with endobronchial tuberculosis (EBTB) with right anterior segment involvement. CASE PRESENTATION: A 95-year-old Caucasian female was evaluated for 1-2 weeks of non-productive cough and new intermittent wheezing. Her symptoms improved with bronchodilators. Past medical history is unremarkable. She lived all her life in Omaha, Nebraska prior to moving to New York State 5 years prior to admission. She is a never smoker, previously worked as a secretary, and her only international travel was to Mexico in the 1960s. Review of systems was negative for hemoptysis, weight loss, fever, chills or chest pain. Physical exam revealed a nourished woman who was not ill appearing with focal crackles in the right anterior parasternal chest. Laboratory exam showed hemoglobin 11.0 g/dL and serum sodium 139 mEq/L. Chest X-ray revealed a right upper lobe opacity, mostly perihilar [Figure 1]. CT chest showed a mass encasing the right upper lobe bronchus leading to anteromedial right upper lobe atelectasis, with multiple right subpleural nodules and right hilar lymphadenopathy [Figure 2]. Bronchoscopy was performed, with bronchial alveolar lavage (BAL) PCR positive for Mycobacterium tuberculosis and Mycobacterium avium complex. Patient was diagnosed with EBTB causing ASTB. She was started on Isoniazid, Pyrazinamide, Ethambutol and Rifampin. Prednisone was used as adjunctive therapy for endobronchial involvement; and after two weeks of therapy her chest x-ray had normalized and she had no local rales or wheezing. DISCUSSION: Both ASTB and EBTB are rare in adults. Cases of ASTB occur more often with primary TB infection in children. Infrequently, reactivation of TB may present as anterior segment disease. Uniquely, our 95-year-old patient also had endobronchial involvement. The prevalence of EBTB is 10-40% in patients with active pulmonary tuberculosis, and 90% of these patients will develop some degree of bronchial stenosis. The pathogenesis of EBTB is unclear, and diagnosis is frequently delayed until bronchial stenosis, atelectasis, and bronchiectasis are present. The most common bronchoscopic finding in EBTB is inflamed mucosa. The use of steroids to minimize bronchial stenosis remains controversial. CONCLUSIONS: Anterior Segment Tuberculosis and Endobronchial Tuberculosis are uncommon presentations of a common disease. Diagnosis is challenging due to rarity in the elderly population, nonspecific clinical presentation, and atypical radiographic findings. Reference #1: Kashyap, Surender et. Al. Endobronchial Tuberculosis. Indian J Chest Dis Allied Sci 2003; 45: 247-256. Reference #2: Rikimaru, Toru. Therapeutic Management of Endobronchial Tuberculosis. Expert Opinion on Pharmacotherapy. Vol. 5, ISS. 7, 2004. Reference #3: Spencer, David et. al. Anterior Segment Upper Lobe Tuberculosis in the Adult: Occurrence in Primary and Reactivation Disease. Chest. Vol 97, ISS.2, 1990. DISCLOSURES: No relevant relationships by richard blinkhorn, source=Web Response No relevant relationships by Hau Chieng, source=Web Response No relevant relationships by Shannon Murawski, source=Web Response No relevant relationships by Biplab Kumar Saha, source=Web Response

PULMONARY HAMARTOMA PRESENTING AS CENTRAL AIRWAY OBSTRUCTION

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: Pulmonary hamartoma (PHM) is the most common benign tumor of the lung with a population incidence of 0.25% (1). Most PHM are intraparenchymal with only 10% being endobronchial (1). We report a case of endobronchial hamartoma presenting as left main stem (LMS) obstruction treated successfully with combination of snare electrocautery, cryotherapy debulking, and argon plasma coagulation (APC). CASE PRESENTATION: A 52-year old woman, never smoker, with history of cough-variant asthma presented with intermittent wheezing and dyspnea on exertion, presumed to be recurrent episodes of acute bronchitis or asthma. She failed a course of antibiotics and initiation of inhaled corticosteroids with beta 2 agonist therapy. Computed tomography (CT) of the chest demonstrated an ovoid mass predominantly in the left upper lobe bronchus (LUL) with partial extension to LMS and post obstructive collapse of the lingula (fig. 1). Hypoperfusion of the left lung was also evident. Bronchoscopy revealed obstruction of LMS bronchus by an endobronchial lesion (fig. 2). Complete excision of the lesion was performed using combination of snare electrocautery, cryotherapy debulking, and APC destruction of the tumor base, noted to be at the bifurcation of apico-posterior segment of the LUL. Histopathology revealed benign cartilage interspersed with a fibrovascular stroma and scattered bronchial glands, consistent with PHM (fig.3). The patient’s symptoms improved significantly following the intervention. She remains symptom-free on a 3-month follow up. DISCUSSION: Hamartomas are disorganized tumor masses composed of various tissues including fat, epithelium, cartilage, and fibrous stroma. PHMs are usually slow growing and most patients are asymptomatic. Classified as either intraparenchymal or endobronchial, the symptoms depend largely on the location of the tumor; small peripheral intraparenchymal tumors often remain asymptomatic for many years, however, endobronchial hamartomas may present as recurrent bronchitis due to post-obstructive inflammation, as did our patient. Chest radiograph may not reveal collapse despite significant obstruction due to air-trapping as a result of ball-valve phenomenon; however, CT chest is diagnostic. Additionally, hypo-perfusion of the under-ventilated lung may be observed due to perfusion shift to better aerated lung.Given their minimal potential for malignant transformation, PHMs are usually managed conservatively. Tumor debulking utilizing multimodal endoscopic ablative techniques, as in our patient, is the preferred modality in patients with symptomatic endobronchial disease (2). CONCLUSIONS: Endobronchial PHM, although a rare entity, should be considered in the differential diagnosis of patients presenting with chronic cough and/or wheezing. CT allows identification of the location and size of the lesion and bronchoscopic excision using multi-modality approach is therapeutic. Reference #1: 1. Ahmed S, Arshad A, Mador MJ. Endobronchial hamartoma; a rare structural cause of chronic cough. Respiratory medicine case reports. 2017;22:224-7. Reference #2: 2. Bilaceroglu S. Endobronchial Ablative Therapies. Clin Chest Med. 2018;39(1):139-48. DISCLOSURES: No relevant relationships by DIVYANSH BAJAJ, source=Web Response No relevant relationships by Rydhwana Hossain, source=Web Response No relevant relationships by Or Kalchiem-Dekel, source=Web Response No relevant relationships by Akshay Kohli, source=Web Response stock holder relationship with Opko Health, Inc Please note: $20001 - $100000 Added 03/02/2018 by Matthew Paparo, source=Web Response, value=dividends Audience for a educational course relationship with Pinnacle Biologics Please note: $1-$1000 Added 03/02/2018 by Matthew Paparo, source=Web Response, value=Honoraria No relevant relationships by Lynette Parker, source=Web Response No relevant relationships by Edward Pickering, source=Web Response No relevant relationships by Ashutosh Sachdeva, source=Web Response

Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942.

BackgroundInterleukin-13 (IL-13) is a key mediator of T-helper-cell-type-2 (Th-2)-driven asthma, the inhibition of which may improve treatment outcomes. We examined the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of VR942, a dry-powder formulation containing CDP7766, a high-affinity anti-human-IL-13 antigen-binding antibody fragment being developed for the treatment of asthma.MethodsWe conducted a phase 1, randomized, double-blind, placebo-controlled, ascending-dose study at Hammersmith Medicines Research, London, UK, which is now complete. Healthy adults aged 18–50 years (n = 40) were randomized 3:1 to a single inhaled dose of VR942 0.5, 1.0, 5.0, 10, or 20 mg, or placebo. Adults aged 18–50 years who were diagnosed with asthma for ≥6 months before screening, and had forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values ≥70% of the predicted values at screening (n = 45), were randomized to once-daily inhaled VR942 0.5 or 10 mg, or placebo (2:2:1), or VR942 20 mg or placebo (3:2), for 10 days. All participants were randomized to receive VR942 or placebo based on a randomization list prepared by an independent HMR statistician using SAS® software (SAS Institute, Cary, NC). The primary outcome was safety and tolerability of VR942 (safety population, defined as all who received at least one dose of VR942 or placebo). This study is listed on ClinicalTrials.gov (NCT02473939).FindingsIn the VR942 and placebo groups, treatment-emergent adverse events (TEAEs) were reported in 10/30 (33%) and 0/10 (0%) healthy participants, and in 16/29 (55%) and 9/16 (56%) participants with asthma, respectively. Mild intermittent wheezing occurred in 7 participants (VR942 20 mg, n = 4; corresponding placebo, n = 3), resolving spontaneously within 1 h. All TEAEs were mild or moderate; there were no deaths, serious adverse events, or clinically significant changes in vital signs, electrocardiograms, or laboratory parameters. There was no clinically significant immunogenicity, with only one participant with asthma considered positive for treatment-related immunogenicity for CDP7766.InterpretationThis study, considered to be the only example of a dry powder anti-IL-13 fragment antibody being administered via inhalation, demonstrated that single and repeat doses were well tolerated over a period of up to 10 days in duration. Rapid and durable inhibition of fractional exhaled nitric oxide (FeNO) (secondary outcome) provided evidence of pharmacological engagement with the IL-13 target in the airways of participants diagnosed with mild asthma. These data, together with the numerical improvements observed for predose FEV1, justify further clinical evaluation of VR942 in a broader population of patients with asthma, and continue to support the development of an inhaled anti-IL-13 antibody fragment as a potential future treatment that is alternative to monoclonal antibodies delivered via the parenteral route.FundingStudy funding and funding for the medical writing and editorial support for preparation of the manuscript were split equally between the two study co-funders (Vectura Ltd and UCB Pharma).

Visual Diagnosis: A 7-year-old Boy with Dyspnea and an Unusual Chest Radiograph

1. Katherine B. Salciccioli, MD* 2. Athar M. Qureshi, MD*,† 3. Hugh D. Allen, MD*,† 1. *Department of Cardiology, Texas Children’s Hospital, Houston, TX 2. †Baylor College of Medicine, Houston, TX A 7-year-old boy presents to his pediatrician with gradually worsening shortness of breath and exercise intolerance over months to years. He was admitted for right-sided pneumonia twice during childhood with seemingly complete recovery each time, but otherwise he has been generally healthy and developmentally appropriate. Current medications include albuterol inhalers taken as needed since early childhood for wheezing during viral illnesses. With the recent worsening of his symptoms, albuterol is again tried without any improvement in his symptoms. He does not have fever, cough, nasal congestion, chest pain, palpitations, vomiting, diarrhea, or weight changes. On physical examination, the patient has normal vital signs. He is small for his age but is following his growth curve appropriately with height in the 15th percentile and weight in the 11th percentile. He has normal findings on head and neck examination. His cardiac examination is notable for a fixed split S2 with no murmurs, rubs, or gallops. He has diminished breath sounds on the right with a soft, intermittent expiratory wheeze and a clear left lung. He has no abdominal organomegaly. Pulses are 2+ and symmetric in all extremities. In addition to his physical examination findings, a chest radiograph (Fig 1) is interpreted as showing dextrocardia, so the patient is referred to the cardiology clinic where echocardiography reveals the diagnosis. Figure 1. Chest radiograph interpreted as dextrocardia, prominent right-sided pulmonary vasculature, and hyperinflation of the left lung. In the cardiology clinic, echocardiography shows the heart located in the right chest, with the cardiac apex pointing leftward, partial anomalous venous return to the inferior vena cava (IVC) (Video 1), and mild right heart dilation (Video 2 …

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDMS-wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.

ANTISYNTHETASE SYNDROME: COURSE OF A RARE DISEASE ON EXAMPLE OF CLINICAL CASE

Systemic disorders of connective tissue refer to rare and poorly studied diseases. This group of diseases associated with the variable course and makes it interesting for either medical scientists and researchers or practitioner. Herein we report a case of antisynthetase syndrome with interstitial lung disease complicated by pulmonary thromboembolism. The patient is 71 year old female, who suffered from severe dyspnea, dry cough, intermittent wheezing. Also she had dry eyes, dry mouth, muscle weakness and intermittent pain in large joints, and low grade fever. Physical examination revealed a characteristic heliotrope eye rash, V sign, «mechanic’s hand», peripheral muscles atrophy, dry eyes and mouth, fine crackles to auscultation in basal parts of lungs, soft S1 and S2 heart sounds. Her biochemical profile showed increased creatinekinase, LDH, AsAT, and AlAT Her immunology results were positive to ANA, anti-ds-DNA, anti-ss-A, anti-ss-B and anti-Jo-1 autoantibodies. Based on the obtained data, antisynthetase syndrome was established. It was detected, that progressive dyspnea had been caused by interstitial lung disease and pulmonary thromboembolism. It was confirmed by chest CT-scan and pulmonary angiography. Treatment in this case is mainly symptomatic. It was prescribed glucocorticoids, immunosuppressant, and anticoagulants. This case illustrates the course of the antisynthetase overlap syndrome and difficulties of it management due to the lack of treatment standards and reliable data of the medicine effectiveness.

Efficacy of Episodic Use of Montelukast in Preschool Children with Intermittent Wheezing

Efficacy of Episodic Use of Montelukast in Preschool Children with Intermittent Wheezing