Eur Respir Research Articles

MTE26.02 EGFR Targeted Therapies: Lessons Learned

MTE26.02 EGFR Targeted Therapies: Lessons Learned

"Lung biopsy in interstitial lung disease: balancing the risk of surgery and diagnostic uncertainty." Vincent Cottin. Eur Respir J 2016; 48: 1274-1277.

"Lung biopsy in interstitial lung disease: balancing the risk of surgery and diagnostic uncertainty." Vincent Cottin. Eur Respir J 2016; 48: 1274-1277.

"Exertional dyspnoea in COPD: the clinical utility of cardiopulmonary exercise testing." Denis E. O'Donnell, Amany F. Elbehairy, Azmy Faisal, Katherine A. Webb, J. Alberto Neder and Donald A. Mahler. Eur Respir Rev 2016; 25: 333-347.

"Exertional dyspnoea in COPD: the clinical utility of cardiopulmonary exercise testing." Denis E. O'Donnell, Amany F. Elbehairy, Azmy Faisal, Katherine A. Webb, J. Alberto Neder and Donald A. Mahler. Eur Respir Rev 2016; 25: 333-347.

A Mirage: Endobronchial Actinomycosis Mimicking Carcinoid Tumor

SESSION TITLE: Fellow Case Report Poster - Lung Pathology SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary actinomycosis is rare infection caused by Actinomyces spp., an anaerobic Gram-positive bacteria. Endobronchial involvement is very rare in pulmonary actinomycosis. We present a case of a 64 year old woman with chronic cough who had an endobronchial lesion mimicking carcinoid tumor. CASE PRESENTATION: 64 year old female with history of emphysema, presented to the emergency room with chronic non-productive for one year. On presentation her vital signs were normal. Physical exam was significant for focal wheezing at right lung base. Chest X-ray was and laboratory data were normal. Computed tomography scan of the chest showed narrowing of the bronchus intermedius with a radiopaque density with no lymphadenopathy. Bronchoscopy revealed narrowing of the bronchus intermedius with a smooth rounded, reddish pedunculated endobronchial mass. Biopsy of the mass revealed no malignancy, and a filamentous, gram positive, acid fast stain negative organism consistent with Actinomyces. Patient received six weeks of intravenous Penicillin, followed by 20 weeks of oral Penicillin VK. Patient returned to pulmonary clinic six months later with resolution of cough. DISCUSSION: Endobronchial actonomycosis is caused by Actinomyces spp., an anaerobic Gram-positive bacteria that normally colonizes the digestive and genital tracts. Pulmonary actinomycosis is more common in males, and results from aspiration of oropharyngeal or gastrointestinal contents. Respiratory symptoms include cough, sputum production, and pleuritic chest pain. Laboratory data will generally be normal. Diagnosis can be challenging, as up to 25% of cases are initially misdiagnosed as malignancy. Diagnostic properties include positive culture and demonstration of sulphur granules, with clinical and radiographic correlation. Fiberoptic bronchoscopy is usually non-diagnostic unless there is clear endobronchial lesion which is biopsied. The lesion will demonstrate an irregular submucosal tumor with granular thickening that is partially obscuring the bronchi. Treatment entails 6 months of penicillin therapy, with tetracycline and erythromycin being second line agents. CONCLUSIONS: Endobronchial actinomycosis is an extremely rare infection resulting from aspiration of oropharyngeal contents. On bronchoscopy it frequently mimics malignancy, and up to 25% of cases are initially misdiagnosed as cancer. Treatment entails a prolonged course of penicillin therapy. Reference #1: Mabeza, G.F., Macfarlane, J., Pulmonary actinomycosis. Eur Respir J 2003; 21: 545-551 DISCLOSURE: The following authors have nothing to disclose: Yuriy Takhalov, John Kileci, Samir Abdelhadi No Product/Research Disclosure Information

Cardiac Arrhythmias as Initial Presentation of Sarcoidosis

SESSION TITLE: Student/Resident Case Report Poster - Cardiovascular Disease I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Cardiac sarcoidosis is an infiltrative disease which is usually clinically silent but occasionally may be the first manifestation of sarcoidosis even in the absence of overt systemic involvement. It frequently presents with structural and conduction abnormalities including supraventricular and ventricular arrhythmias, myocardial damage simulating infarction, heart failure, cardiomyopathy, valvular heart disease, and sudden death. CASE PRESENTATION: A 33 year old African American female presented to emergency room with episodes of palpations. Her exam and laboratory work up were unremarkable. Electrocardiogram showed sinus arrhythmia with pre-ventricular contractions and she was started on Metoprolol. She was having non-sustained ventricular tachycardia (NSVT) which subsequently became sustained requiring Lidocaine with conversion to sinus tachycardia. Echocardiography was normal. However she continued to have NSVT which raised a concern for an infiltrative process. She had cardiovascular magnetic resonance imaging (CMRI) which showed a large area of delayed mid myocardial enhancement at the inferolateral, basal, mid portion and apical wall with 25% viability and hypokinesis. A high resolution computed tomography of her chest was unrevealing. Endomyocardial biopsy (EMB) was considered as she had no other obvious manifestation of sarcoidosis but was not done as her lesions were patchy. She eventually got an Implantable Cardioverter-Defibrillator and was discharged on Metoprolol. DISCUSSION: The diagnosis and management of cardiac sarcoidosis is a major challenge especially in the absence of systemic manifestations. Findings on electrocardiogram and echocardiogram are nonspecific; CMRI and even positron emission tomography (PET) features may be suggestive but are not diagnostic. EMB which demonstrates noncaseating epithelioid granulomas lacks sensitivity as it may miss the lesion and is usually reserved for patients without histologic confirmation from another source. The ability to diagnose this promptly, predict progression and prognosis, and intervene before a fatal cardiac event, deserves further investigation. The use of steroids lack confirmatory randomized clinical trials. A low threshold for invasive procedures is suggested due to the risk of sudden death. CONCLUSIONS: In young patients presenting with cardiac arrhythmias, sarcoidosis should be considered even in the absence of systemic involvement as this might be a herald sign for an opportunity to intervene and prevent impending sudden cardiac death. Reference #1: Schulte W, Kirsten D, Drent M, Costabel U.Cardiac involvement in sarcoidosis. Eur Respir Mon. 2005;32:130 Reference #2: Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, et al. Detection of myocardial damage in patients with sarcoidosis. Circulation. 2009;120(20):1969. Reference #3: Nery PB, Leung E, Birnie DH. Arrhythmias in cardiac sarcoidosis: diagnosis and treatment. Curr Opin Cardiol. 2012;27(2):181. DISCLOSURE: The following authors have nothing to disclose: Chukwunweike Nwosu, Deepika Nandiraju, Danila Deliana, Joseph Neri No Product/Research Disclosure Information

A Rare Case of Hemoptysis Due to Pyogenic Granuloma in Lung

SESSION TITLE: Student/Resident Case Report Poster - Signs and Symptoms of Chest Disease SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Introduction: Hemoptysis is expectoration of blood which can vary between minimal blood streaking of the sputum to massive hemoptysis.1 2 Common causes for hemoptysis are acute bronchitis, bronchiectasis, neoplasm, infection, coagulopathy, iatrogenic, autoimmune conditions and pulmonary embolism. In about 30% of the cases it can be cryptogenic in nature.3 We present a rare case of hemoptysis secondary to pyogenic granuloma in the lung. CASE PRESENTATION: Case: A 74 yo Caucasian male presented to the emergency room with symptoms of acute hemoptysis. He woke up at middle of night with symptoms of acute cough and he noticed bright red blood about a 10-15ml. He had repeated episodes of hemoptysis in the ER. He did not have any symptoms of fever, chills or sweating. Past medical history: No history of prior hemoptysis. He had history of CAD with CABG. Medications: Plavix 75 mg daily and aspirin 81mg daily. Family history: Lung cancer in sister. Social history: Remote history of chewing tobacco. Exposure to asbestos. On examination: Pulse: 116/min. Sat: 97% on 3L oxygen Chest: crackles in right lung base. Chest was resonant on percussion. CTA chest: No PE. Alveolar opacities in the right lower lobe. Bronchoscopy: Revealed large blood clot in right lateral basal sub segment which was suctioned. There was small area of submucosal abnormality which was dark purple color and about a centimeter in size without any elevation above the mucosal layer. Endobronchial biopsy was done from the mucosa to rule out malignancy. Broncho-alveolar lavage and washings were negative for AFB, fungus and bacteria. Biopsy: Revealed normal mucosa with proliferation of the small capillary sized blood vessels resembling pyogenic granuloma. No malignant cells were seen. Final diagnosis: Hemoptysis due to pyogenic granuloma in the right lower lobe submucosal layer. DISCUSSION: Discussion: Pyogenic granuloma is a benign vascular tumor of the skin and the mucous membrane characterized by friable surface. It can occur at any age and it is seen more often in children and young adults. In a review of 325 cases 86% of the lesions were in the skin and 14% in mucosal layer. It is predominantly seen in the head and neck area with predominance in the lip and gingival mucosa.4 Common treatments for cutaneous lesions include surgery with excision or curettage, laser treatment, cryotherapy or topical or intraepithelial therapy with sclerotherapy, intralesional corticosteroids, bleomycin and ligation. No cases have been reported with occurrence in the endobronchial mucosal layer. There is no defined treatment modalities for pyogenic ganuloma in the lung. If there is recurrence or persistence of hemoptysis treatment modalities like laser or cryotherapy may be helpful in distal lesions. CONCLUSIONS: Hemoptysis can occur due to rare conditions like pyogenic granuloma in the lung. Reference #1: Eur Respir J. 2008;32(4):1131. Reference #2: Emerg Med Clin North Am. 2003 May;21(2):421-35. Reference #3: Am J Respir Crit Care Med. 2007;175(11):1181. DISCLOSURE: The following authors have nothing to disclose: Shweta Kambali, Mohd Kanjwal, Shrinivas Kambali No Product/Research Disclosure Information

WITHDRAWN: Treatment Effect of Combination of Nsaid and Antitussives in Patients With URTI-Related Cough

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Eur Respir J. 46 (2015) PA3852, http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Systemic Mastocytosis With Pulmonary Involvement

SESSION TITLE: Fellow Case Report Slide: Pulmonary Critical Care Disorders: Think Twice SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Sunday, October 23, 2016 at 10:45 AM - 12:00 PM INTRODUCTION: Mastocytosis is a rare disorder that involves mast cell infiltration in a range of organs. Pulmonary involvement is an even rarer entity. Here we present a case of a patient with systemic mastocytosis with asymptomatic pulmonary involvement. CASE PRESENTATION: The patient is a 68 year old male who was referred to primary clinic to establish care. He recently presented to the emergency room for abdominal pain of seven months duration. There he was diagnosed with gallstones and an inguinal hernia and discharged with primary care followup. The only other complaint the patient had was persistent pruritus for over one year. On review of systems the patient was noted to have weight loss. He denied any cough or shortness of breath. On exam the patient was cachectic with numerous skin excoriations from scratching. He had mild right upper quadrant tenderness, hepatomegaly, and a reducible inguinal hernia. Labs were notable for an alkaline phosphatase of 652 IU/L and a leukocytosis of 11.8 cells per mL with 29% eosinophils. Serum tryptase was significantly elevated at 130 ng/mL. Abdominal ultrasound demonstrated hepatomegaly with coarse lobulated surface suggestive of chronic liver disease. A chest X-ray obtained during his emergency room visit was notable for diffuse reticular opacities. Chest CT showed pulmonary nodules and hilar lymphadenopathy. Liver biopsy and EBUS were performed with pathology consistent with systemic mastocytosis. DISCUSSION: Systemic mastocysotosis is a rare disease and involvement of the skeletal muscle, gastrointestinal tract, and lymph nodes is common. Pulmonary involvement is less common and may occur in less than 20% of patients with systemic mastocytosis. Symptoms can include cough, dyspnea, and asthma like symptoms. Findings on chest radiograph include interstitial fibrosis and pulmonary nodules. CT findings include nodular and reticular opacities as well as mediastinal lymph node enlargement. CONCLUSIONS: Pulmonary involvement is a rare manifestation of systemic mastocytosis. The disease can present with a wide range of findings on chest radiograph and CT. Symptoms can vary between being asymptomatic to having mild asthma like symptoms. Reference #1: Avila N. A. et al. 1996. Pulmonary and Ovarian Manifestations of Systemic Mastocytosis. AJR; 166: 969-970. Reference #2: Kelly A. M. et al. 2004. HRCT Appearance of Systemic Mastocytosis Involving the Lungs. J Thoracic Imaging; 19: 52-55. Reference #3: Schmidt M. et al. 2000. Pulmonary manifestation of systemic mast cell disease. Eur Respir J; 15: 623 - 625. DISCLOSURE: The following authors have nothing to disclose: Ray Pillai, Darren Maehara, Nishay Chitkara No Product/Research Disclosure Information

Chronic Necrotizing Aspergillosis

SESSION TITLE: Student/Resident Case Report Poster - Chest Infections I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Chronic Necrotizing Aspergillosis (CNA) is a term used to define an indolent, locally invasive form of pulmonary aspergillosis that often presents in the upper lobes among patients with either preexisting lung disease or immune suppression. It is usually characterized by chest pain, cough, sputum production, hemoptysis, and fatigue. Slow progression of disease is best characterized on CT scan. CASE PRESENTATION: A 58-year-old woman with ulcerative colitis (UC) on infliximab, initiated five months previous, and no history of lung disease presented with diarrhea, fatigue, and weight loss of a few weeks duration. Though she denied pulmonary complaints, save a chronic dry cough, CT of the abdomen revealed new cavitary lesions of the right lower lobe that were not present on previous CT. Her serum beta-d-glucan was >500 pg/mL. A bronchoaveolar lavage (BAL) galactomannan returned at 10.65 ng/mL. Serum antineutrophil cytoplasmic antibody titers, as well as histoplasma antigen, cultures for acid fast bacilli, viruses, and Legionella from her BAL returned negative. Fungal cultures grew Aspergillus niger. She was treated with voriconazole. CT at her three month follow up showed near-complete resolution of her cavitary lesions. DISCUSSION: Due to the nebulous nature of the disease, the diagnosis of CNA is often difficult. BAL, transbronchial, and percutaneous aspirates often fail to grow fungi. A diagnosis generally requires a combination of Aspergillus serology, radiographic evidence, and constitutional symptoms with exclusion of other common causes of cavitary lung lesions. BAL galactomannan is more specific for the diagnosis of pulmonary aspergillosis than a serum sample, especially if used at a higher cut off than the FDA standard. In a meta-analysis, a 1 ng/mL cutoff of galactomannan in fluid from a BAL yielded a sensitivity and specificity of 85% and 94% respectively, with a positive likelihood ratio of 14.29. CONCLUSIONS: Given the slowly progressive nature of CNA, diagnosis at an early stage can be difficult without a high degree of clinical suspicion. The initial nonspecific symptoms of weight loss and fatigue were initially thought secondary to her UC. It is fortunate that the CT abdomen detected the atypical presentation of lower lobe pulmonary cavities preventing treatment with high-dose steroids combined with continuing cycles of infliximab, which would have lead to disseminated aspergillosis and significant morbidity or death. It is essential to have a high clinical suspicion for opportunistic infections, such as CNA, in immunosuppressed patients as they are both at increased risk and more likely to manifest with an atypical presentation. Reference #1: Kousha, M., R. Tadi, and A.O. Soubani, Pulmonary aspergillosis: a clinical review. Eur Respir Rev, 2011. 20(121): p. 156-74. Reference #2: Guo, Y.L., et al., Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest, 2010. 138(4): p. 817-24. DISCLOSURE: The following authors have nothing to disclose: Jeremy Gentile, Anne Chen No Product/Research Disclosure Information

"Advanced medical interventions in pleural disease." Rahul Bhatnagar, John P. Corcoran, Fabien Maldonado, David Feller-Kopman, Julius Janssen, Philippe Astoul and Najib M. Rahman. Eur Respir Rev 2016; 25: 199-213.

"Advanced medical interventions in pleural disease." Rahul Bhatnagar, John P. Corcoran, Fabien Maldonado, David Feller-Kopman, Julius Janssen, Philippe Astoul and Najib M. Rahman. Eur Respir Rev 2016; 25: 199-213.

"Malignant pleural effusion: from bench to bedside." Ioannis Psallidas, Ioannis Kalomenidis, Jose M. Porcel, Bruce W. Robinson and Georgios T. Stathopoulos. Eur Respir Rev 2016; 25: 189-198.

"Malignant pleural effusion: from bench to bedside." Ioannis Psallidas, Ioannis Kalomenidis, Jose M. Porcel, Bruce W. Robinson and Georgios T. Stathopoulos. Eur Respir Rev 2016; 25: 189-198.

Predicting Obstructive Sleep Apnea with Periodic Snoring Sound Recorded at Home.

The cost-effectiveness of diagnosing obstructive sleep apnea (OSA) could be improved by using a preliminary screening method among subjects with no suspicion of other sleep disorders. We aimed to evaluate the diagnostic value of periodic snoring sound recorded at home. We included 211 subjects, aged 18-83 (130 men), who were referred to our laboratory for suspicion of OSA, and had a technically successful overnight polygraphy, measured with the Nox T3 Sleep Monitor (Nox Medical, Iceland) with a built-in microphone. We analyzed the percentage of periodic snoring during the home sleep apnea study. Apnea-hypopnea index (AHI) ranged from 0.1 to 116 events/h and the percentage of periodic snoring from 1% to 97%. We found a strong positive correlation (r = 0.727, p < 0.001) between periodic snoring and AHI. The correlation was slightly stronger among female, younger, and obese subjects. The best threshold value of the periodic snoring for predicting an AHI > 15 events/h with as high sensitivity as possible was found to be 15%. There, sensitivity was 93.3%, specificity 35.1%, and negative predictive value 75.0%. According to our results, it is possible to set a periodic snoring threshold (15% or more) for the subject to advance to further sleep studies. Together with medical history and prior to more expensive studies, measuring periodic snoring at home is a simple and useful method for predicting the probability of OSA, in particular among women who are often unaware of their apnea-related snoring.

"Exercise pulmonary haemodynamics: a test in search of purpose." J. Gerry Coghlan and Harm Jan Bogaard. Eur Respir J 2016; 47: 1315-1317.

"Exercise pulmonary haemodynamics: a test in search of purpose." J. Gerry Coghlan and Harm Jan Bogaard. Eur Respir J 2016; 47: 1315-1317.

PWE-018 Predictive Factors for An Indeterminate Result on Interferon-Gamma Release Assay

Introduction Interferon-gamma (IFN-γ) release assay is used to identify patients with latent tuberculosis prior to biological treatment initiation. A lack of stimulation capacity of lymphocytes by the test control results in an indeterminate result. This is not uncommon in inflammatory bowel disease (IBD) patients receiving immunosuppressive agents. 1,2,3 The aim of this study is to compare the clinical and laboratory characteristics of patients with indeterminate results to those with determinate results. Methods The national database of IBD patients receiving biological agents was accessed. IFN-γ release assay (QuantiFERON-TB Gold) results were noted. Parameters at the time of testing were collected, namely age, diagnosis, disease activity, blood results and drug treatment. Comparisons between the indeterminate group and determinate group were made using IBM® SPSS® Statistics Version 20. The study was approved by the University and Research Ethics Committee of Malta. Results Data from 136 subjects was analysed. 8.8% ( n = 12) had an indeterminate IFN-γ release assay result, 2.2% ( n = 3) had a positive result, while 89% ( n = 121) had a negative result. The indeterminate group had a significantly lower lymphocyte count ( p = 0.041), globulin level ( p = 0.042), immunoglobulin A (IgA) ( p = 0.031) and haemoglobin ( p = 0.016). C-reactive protein was higher in the indeterminate group ( p = 0.024). No significant differences were recorded for age, gender, diagnosis, disease activity, white cell count, neutrophils, platelets, renal/liver function, albumin levels, IgM, IgG, or drug treatment. Critically, only 25% of indeterminate result subjects had a repeat test, all reported as negative. Conclusion Indeterminate results are common in IBD patients, affecting nearly 1 in 10 patients. Patients with low lymphocyte counts, low globulin, low haemoglobin, low IgA and high CRP levels are more likely to have an indeterminate result when tested. The potential of a false negative result is likely to be higher in these patients. One must exert caution when requesting IFN-γ release assays in such IBD patients since the probability of a determinate result may be low. We advise test repetition in all patients with indeterminate results and screening with chest x-ray. References 1 Helwig U, Muller M, Hedderich J, et al, Corticosteroids and immunosuppressive therapy influence the result of QuantiFERON TB Gold testing in inflammatory bowel disease patients . J Crohns and Colitis 2012; 6 :419–424. 2 Jeong SJ, Han SH, Kim CO, et al, Predictive factors for indeterminate result on the QuantiFERON test in an intermediate tuberculosis-burden country . J Infect . 2011; 62 :347–354. 3 Kobashi Y, Sugiu T, Mouri Y, et al , Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice . Eur Respir J 2009; 33 :812–815. Disclosure of Interest None Declared

"Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis." Yael Gernez, Jeffrey Waters, Bojana Mirković, Gillian M. Lavelle, Colleen E. Dunn, Zoe A. Davies, Cassie Everson, Rabindra Tirouvanziam, Elana Silver, Sylvan Wallenstein, Sanjay H. Chotirmall, Noel G. McElvaney, Leonore A. Herzenberg and Richard B. Moss. Eur Respir J 2016; 47: 177-185.

"Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis." Yael Gernez, Jeffrey Waters, Bojana Mirković, Gillian M. Lavelle, Colleen E. Dunn, Zoe A. Davies, Cassie Everson, Rabindra Tirouvanziam, Elana Silver, Sylvan Wallenstein, Sanjay H. Chotirmall, Noel G. McElvaney, Leonore A. Herzenberg and Richard B. Moss. Eur Respir J 2016; 47: 177-185.

WITHDRAWN: Combination of NSAID and Antitussives in Treatment of URTI Related Cough: An Observational Study

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Eur Respir J. 46 (2015) PA3852, http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

“Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension.” Irene M. Lang and Sean P. Gaine. Eur Respir Rev 2015; 24: 630–641.

“Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension.” Irene M. Lang and Sean P. Gaine. <i>Eur Respir Rev</i> 2015; 24: 630–641.

PC-FACS

PC-FACS

Lower Airway Obstruction Is Associated with Increased Vaso-Occlusive Pain Episodes in Adults with Sickle Cell Anemia

Background: Vaso-occlusive pain episodes (VOE) are the most common complication and reason for hospital admission in individuals with Sickle Cell Anemia (SCA). Recently our team demonstrated that in adults with SCA followed prospectively for approximately 5 years, a lower baseline Forced Expiratory Volume in 1 second percent predicted (FEV1%), which is associated with earlier mortality, but evidence of obstructive or restrictive lung function patterns is not (Blood 2015, in press). Based on the evidence that abnormal pulmonary function is associated with earlier mortality, we tested the hypothesis that baseline pulmonary function patterns were associated with SCA-related morbidity, including VOE and acute chest syndrome (ACS) events.Procedure: A prospective cohort of adults with SCA followed in the Cooperative Study for Sickle Cell Disease (CSSCD) was constructed based on a planned secondary analysis. Data from the first PFT record at age 21 and older were used for this study. Percent predicted values were determined for each participant based on their age, gender, height, and race for FEV1 and the ratio of FEV1 to forced vital capacity (FEV1/FVC) using the Global Lung Function 2012 equations (Eur Respir J, 2012; 40(6): 1324-1343). Assessment of lower airway obstruction was based on % predicted FEV1/FVC. Percent predicted total lung capacity (TLC), a measure of restrictive lung disease, was determined using published equations and corrected based on race. All PFT evaluations were checked for quality. Negative binomial regression models were used to determine the association between future VOE, ACS events, and spirometry measurements after adjusting for age, sex, hemoglobin, and fetal hemoglobin levels.Results: A total of 430 adults with SCA were evaluated. Ages of the study participants ranged from 21.7-66.4 years with a median age of 32.6 years at the time of first PFT and median follow-up was 5.5 years. Only FEV1/FVC% predicted as a continuous covariate was a significant predictor of future VOE. Lower FEV1/FVC% predicted was associated with higher future pain event rates with a rate ratio of 1.022 (95% CI 1.002 - 1.042; p=0.028). For every 10% decrease in FEV1/FVC% predicted there is a 23% increase in the rate ratio. TLC% predicted did not predict future VOE (p=0.762). FEV1/FVC% predicted or TLC% predicted did not predict future ACS events (p=0.618 and p=0.430 respectively). When FEV1/FVC% predicted and TLC% predicted < 5th percentile were used in the regression equation instead of continuous values, neither abnormal lung function parameter was associated with an increased incidence of VOE or ACS events.Conclusions: For the first time, we have demonstrated that spirometry evaluation with FEV1/FVC% predicted, as a measure of lower airway obstruction, identifies a group of adults with SCA at increased risk for future vaso-occlusive pain episode.Table 1CovariateRate Ratio (95% CI)PAge at PFT*-.112 (.850, .941).000Male1.032 (.581, 1.836).914Average Fetal Hemoglobin.985 (.894, 1.085).754Average Hemoglobin.954 (.763, 1.193).682Negative FEV1/FVC percent predicted**.022 (1.002, 1.042).028Final Negative Binomial Regression model for vaso-occlusive pain episodes after lung function testing (N= 430)*PFT is Pulmonary Function Test** Negative FEV1/FVC percent is reverse-coded so that lower values are associated with rate ratios above 1. DisclosuresNo relevant conflicts of interest to declare.

Exhaled Nitric Oxide During Infancy as a Risk Factor for Asthma and Airway Hyperreactivity

D Chang, W Yao, CJ Tiller. Eur Respir J. 2015;45(1):98–106 To determine whether exhaled nitric oxide (eNO), lung function, airway reactivity, allergen sensitization, and cytokines measured during infancy are predictors of asthma at age 5 years. The study participants included 116 infants and toddlers with eczema. The median age was 10.7 months (range 2.6–19.1 months). Participants were enrolled before the development of wheezing illness. There were 90 study participants, the majority of whom were white, at follow-up (5 years of age), and 68% had a diagnosis of asthma. In this longitudinal study of a US cohort, measures were obtained …