Selective Myeloid Depletion of Galectin-3 Offers Protection Against Acute and Chronic Lung Injury

Rationale: Galectin-3 (Gal-3) is an immune regulator and an important driver of fibrosis in chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Previous work has shown that global deletion of galectin-3 reduces collagen deposition in a bleomycin-induced pulmonary fibrosis model (MacKinnon et al., Am. J. Respir. Crit. Care Med., 2012, 185, 537–46). An inhaled Gal-3 inhibitor, GB0139, is undergoing Phase II clinical development for idiopathic pulmonary fibrosis (IPF). This work aims to elucidate the role of Gal-3 in the myeloid and mesenchymal compartment on the development of acute and chronic lung injury.Methods:LgalS3fl/fl mice were generated and crossed with mice expressing the myeloid (LysM) and mesenchymal (Pdgfrb) cre drivers to yield LysM-cre+/-/LgalS3fl/fl and Pdgfrb-cre+/-/LgalS3fl/fl mice. The response to acute (bleomycin or LPS) or chronic (bleomycin) lung injury was compared to globally deficient Gal-3−/− mice.Results: Myeloid depletion of Gal-3 led to a significant reduction in Gal-3 expression in alveolar macrophages and neutrophils and a reduction in neutrophil recruitment into the interstitium but not into the alveolar space. The reduction in interstitial neutrophils corelated with decreased levels of pulmonary inflammation following acute bleomycin and LPS administration. In addition, myeloid deletion decreased Gal-3 levels in bronchoalveolar lavage (BAL) and reduced lung fibrosis induced by chronic bleomycin. In contrast, no differences in BAL Gal-3 levels or fibrosis were observed in Pdgfrb-cre+/-/LgalS3fl/flmice.Conclusions: Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation.

Prognostic Implication of Diagnostic Confidence Level in Patients with Fibrotic Hypersensitivity Pneumonitis

<b><i>Background:</i></b> Hypersensitivity pneumonitis (HP) has various clinical courses and outcomes, but the prognostic factors are not well-defined. Vasakova et al. [Am J Respir Crit Care Med. 2017 Sep;196(6):680–9] have proposed a diagnostic algorithm that categorized suspected patients according to the level of confidence in the diagnosis. This study aimed to investigate whether the confidence level of clinical diagnosis has prognostic implication in patients with fibrotic HP. <b><i>Methods:</i></b> This study included 101 biopsy-proven fibrotic HP patients diagnosed between 2002 and 2017. The patients were retrospectively classified into confident, probable, possible, and unlikely chronic HP, according to the confidence level in the diagnostic criteria/algorithm. The survival and forced vital capacity (FVC) changes were compared between the groups. Risk factors for mortality were analysed using a Cox proportional hazard model. <b><i>Results:</i></b> The median follow-up duration was 67.6 months. The mean age was 60.4 years, and percentages of women were 60.4%. When classified based on the diagnostic criteria/algorithm, possible HP was the most common (51.5%), followed by probable (26.7%), confident (9.9%), and unlikely HP (6.9%). Distinctive survival curves were found according to the diagnostic confidence level, showing the worst outcome in unlikely chronic HP (median survival, 30.2 months). In a multivariable Cox analysis, unlikely HP was a significant predictor of poor survival (hazard ratio, 4.652; 95% confidence interval, 1.231–17.586; <i>p</i> = 0.023), after adjustment for age, body mass index, FVC, and diffusing capacity. <b><i>Conclusions:</i></b> The diagnostic confidence level may predict clinical outcomes in patients with HP. Unlikely HP was shown to have a significantly poorer survival than other diagnostic confidence levels.

AB0047 CLINICAL AND RADIOLOGICAL CHARACTERISTICS AND TREATMENTS OF A COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS AND DIFFUSE INTERSTICIAL PULMONARY DISEASE FOLLOWED AT THE VIRGEN MACARENA UNIVERSITY HOSPITAL

Background:Diffuse interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA)1,2. The most common pattern is the usual interstitial pneumonia (UIP), conditioning a worse prognosis3.Objectives:To describe epidemiological, clinical, and radiological characteristics and treatment used in a cohort of patients diagnosed with RA and ILD.Methods:Retrospective descriptive study, including patients with a diagnosis of RA and ILD, reviewed in the Rheumatology and Pneumology consultations of the Virgen Macarena University Hospital, from 2010 to 2019. Data obtained from medical records are analyzed. SPSS statistical software is used.Results:26 patients were included, 18 women (69.2%). Median age at diagnosis of ILD was 62 years (53-73). Twelve patients (46.6%) used to smoke. The mean time from RA diagnosis to ILD diagnosis was 79 months (8-264). The RF was positive in 91.3% cases (21) and 87% of them (20) were ACPA positive. Fourteen patients (53.8%) had erosions and 3 (11.5%) had an associated Sjögren’s Syndrome. When ILD was diagnosed, the RA activity by DAS28PCR was moderate (3.28; 2.34-3.28) and 13 patients (54.1%) suffered from dyspnea. The mean value of FVC and DLCO in the first assessment was 84% (63-108) and 71.7% (64-86), respectively. The most frequent radiological pattern of ILD was NINE in 15 patients (57.7%), 6 of them (23.1%) had UIP and 5 (19.3%) presented other patterns. Prior to ILD diagnosis, 24 (92.3%) patients received oral glucocorticoids, 18 (69.2%) cases started treatment with c-DMARD and 11 (42.3%) of them with b-DMARD; the most widely used were methotrexate (MTX) in 17 patients (65.4%) and anti-TNFα in 10 (38.5%). After diagnosis, treatment was changed to 12 patients (46.6%); the most used DMARD was leflunomide, in 11 (42.3%), MTX was maintained in 7 patients (26.9%); the number of anti-TNFα used decreased to 4 cases (15.4%), using instead drugs such as rituximab 5 (19.2%), abatacept 3 (11.5%), baricitinib 2 (7.7%) and anti-IL6 2 (7, 7%). During follow-up, 11 cases (57.9%) remained radiologically stable. A slight deterioration in DLCO was observed (66%; 51-80) and there was one death due to lung disease (UIP).Conclusion:In this study, the most frequent radiological pattern was NINE. Half of the patients used to smoke. At the diagnosis of ILD (at ILD diagnosis), dyspnea was the most relevant clinical symptom, with a slight deterioration in the? respiratory function tests. This represented a change in the therapeutic strategy.References:[1]Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011;183:372-78.[2]Fragoulis GE, Nikiphorou E, Larsen J, Korsten P and Conway R. Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front. Med. 2019;6:238.[3]Tanaka N, Kim JS, Newell JD, et al. Rheumatoid arthritis-related lung diseases: CT findings. Radiology. 2004;232:81-91.Disclosure of Interests:None declared

AB0458 SURVIVAL OF SCLERODERMA PATIENTS WITH INTERSTITIAL LUNG DISEASE: OBSERVATION DATA FROM A MALAYSIAN TERTIARY CENTRE

Background:Interstitial lung disease (ILD) is the leading cause of death in scleroderma (SSc) with decline in FVC as a predictor of mortality in patients with SSc-ILD, especially in the early course of the disease.Objectives:The aim of this study is to determine the survival rate of SSc-ILD in a Malaysian cohort of patients from University Malaya Medical Centre (UMMC).Methods:61 patients clinically diagnosed with SSc-ILD were identified and prospectively recruited. Baseline demographic data were collected. Kaplan-Meier analysis was used to estimate the survival.Results:Females were predominant (56, 91.8%). 39 (64%) had limited cutaneous SSc. Majority were ethnicity Chinese 30 (49.2%), followed by Malays 20 (32.8%), Indians 7 (11.4%) and others 4 (6.6%). Mean age was 56.25 (SD ± 12.5) years while mean duration of disease (non-Raynaud’s disease onset) was 10.5 years (SD ± 9.2) (range of 1 year to 44 years) years. 29 (47.5%) patients were positive for anti-ScL-70, whereas 6 (9.8%) patients were anti-centromere positive. There were 16 (26.2%) deaths. Median survival was 24 years. Patients had a sharper drop in survival probability for the first 10 years compared to the next 20 years (Figure 1). Median survival in limited subset was 24 years whereas in diffuse subset was 11 years. Patients from the limited subset appeared to have higher chance of surviving for 10 years and above, compared to those in the diffuse subset (Figure 2).Conclusion:The results demonstrate the poor survival in SSc-ILD patients. The survival rate tends to be worse in the first 10 years of SSc disease duration. Survival rate was poorer in patients with diffuse cutaneous subset.References:[1]Parelas A et al. Lancet Resp Med 2020[2]Goh NS et al. Am J Respir Crit Care Med 2008Disclosure of Interests:JASMIN RAJA Speakers bureau: For Boehringer Ingelheim for topic on Scleroderma-ILD, Grant/research support from: From Boehringer Ingelheim for scleroderma research, Shantini Muthusamy: None declared., CHOUNG MIN NG: None declared.

Level of Mycobacteria in Pre-Treatment Sputum and Susceptibility of M. tuberculosis Strains Isolated from Patients with non-Multidrug-Resistant Pulmonary Tuberculosis AFB (+) and Factors Influencing MGIT Results after the First 8 Weeks of Anti-Tuberculosi

Vietnam is among 30 high TB ​​burden countries even though the Vietnam National TB Program has made great efforts to detect and treat tuberculosis. Objectives: Assessment of Mycobacterial level in sputum before treatment, and susceptibility to the first line anti-TB drugs of M. tuberculosis strains isolated from TB patients with AFB (+) and non-multidrug-resistant. Moreover, factors influencing MGIT outcome after the first 8 weeks of first-line anti-TB drugs therapy in patients with pulmonary tuberculosis was also analysed. Methodology: An observational, analytical study was performed in 128 patients with non-multidrug-resistant pulmonary tuberculosis AFB (+) for evaluating the level of Mycobacteria in sputum before treatment by smear microscopy method; the susceptibility of M. tuberculosis isolated from sputum of the patient was analysed by Lowenstein - Jensen method. Factors affecting positive MGIT results after 2 months of treatment were determined by multivariate logistics regression. Results: The patients had AFB 3+ were 28% in new cases and 24,5% retreatment patients. The rate of M. tuberculosis strains was susceptible to the first line anti-TB drugs in new cases was higher than retreatment patients. The percentage of any anti-TB drug resistance in retreatment tuberculosis was 59,6%, higher than that of new case TB (23,6%). There was high rate of M. tuberculosis strains resistant to Streptomycin and Isoniazid (12,5% and 16,8% for new cases; 42,3% and 36,5% for retreatment cases, respectively). Large radiographic chest lesions and high AFB levels in pre-treatment sputum were factors associated with a positive MGIT result after the first 8 weeks of treatment. Conclusion: Most of TB patients had high level of Mycobacteria in sputum samples collected before treatment. The percentage of M. tuberculosis strains isolated from sputum of pulmonary non MDR-TB patients had any anti-TB drug resistance were high. High Mycobacteria level in pre-treatment sputum and radiographic chest lesions related to positive MGIT result after the first 8 weeks of treatment. Keywords Pulmonary tuberculosis, first-line anti-TB drugs, anti-TB drug resistance, susceptibility, M. tuberculosis. References [1] World Health Organization, Global Tuberculosis Report 2020. Tuberculosis profiles: Viet Nam (2020) Available: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&entity_type=%22country%22&lan=%22EN%22&iso2=%22VN%22 (accessed 10 April 2020).[2] L.T. Luyen, N.V. Hung, Methods for Diagnosis in Tuberculosis, in Le Thi Luyen (Ed), Tuberculosis - Textbook for General Medical Students. Vietnam National University Press, Hanoi, 2020, pp: 47-69 (in Vietnamese).[3] Ministry of Health - National Tuberculosis Programme Guideline for Standard Operating Procedures of Microbiology Laboratory Methods for Mycobacteria. Vietnam National Tuberculosis Programme, Hanoi (2013) (in Vietnamese).[4] Ministry of Health (2018) Guideline for Management, Diagnosis and Treatment for Tuberculosis. (in Vietnamese) Available: https://kcb.vn/vanban/quyet-dinh-so-3216-qd-byt-ngay-23-5-2018-ve-viec-ban-hanh-huong-dan-chan-doan-dieu-tri-va-du-phong-benh-lao (Accessed 12 January 2019)[5] A.P. Ralph, M. Ardian, A. Wiguna et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010 Oct;65(10):863-869. https://doi.org/10.1136/thx.2010.136242[6] C.T. Minh, L.T. Luyen, N.T.L. Huong et al. Plasma concentration of anti-tubeculosis drugs in pulmonary tuberculosis patients, who treatment in National Tuberculosis and Lung Diseases Hospital 2008 Journal of Practical Medicine 651(2009) 50-53 (in Vietnamese).[7] N.V. Nhung, N.B. Hoa, D.N. Sy, C.M. Hennig, A.S. Dean (2015) The fourth national anti-tuberculosis drug resistance survey in Viet Nam. Int J Tuberc Lung Dis. Jun 2015 19(6) 670-675. https://doi.org/10.5588/ijtld.14.0785[8] N.T. Hang, S. Maeda, L.T. Lien, et al. Primary drug-resistant tuberculosis in Hanoi, Viet Nam: present status and risk factors. PloS one 8(8) (2013) e71867. https://doi.org/10.1371/journal.pone.0071867[9] R. Hafner, J.A. Cohn, D.J. Wright, et al. Early bactericidal activity of isoniazid in pulmonary tuberculosis. Optimization of methodology. The DATRI 008 Study Group. Am J Respir Crit Care Med 156 (1997) 918–923. https://doi.org/10.1164/ajrccm.156.3.9612016[10] A. Jindani, V.R. Aber, E.A. Edwards, D.A. Mitchison. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am J Respir Crit Care Med. 121(1980)(6) 939-949. Available: https://www.atsjournals.org/doi/10.1164/arrd.1980.121.6.939 (Accessed 12 January 2019).[11] H.L. Rieder. Intervention for Tuberculosis Control and Elimination. International Union of Tuberculosis and Lung Diseases, Paris, France, 2002.

Analysis of Direct Treatment Cost for Exacerbation of Chronic Obstructive Pulmonary Disease in E Hospital from October 2019 to March 2020

This study analyzes the direct treatment cost for exacerbation of chronic obstructive pulmonary disease (COPD) at the Department of Pulmonology, E Hospital from October 2019 to March 2020. The study results show that the average direct treatment cost for exacerbation of COPD was VND 9,102,311.71; the highest cost was VND 36,304,614 and the lowest cost, VND 2,309,961. Among the direct treatment cost components, drug cost showed the highest proportion, followed by hospital bed, then surgical procedures, tests, diagnostic imaging, functional exploration, examination and medical supplies. The cost of antibiotics accounted for 57.76% of the drug cost. The average number of hospitalization days was 10.77, closely relating to the direct cost. Besides, age and comorbidity also affected the number of hospitalization days. The average health insurance support for each patient was up to 94.46% of the total treatment cost. The results also show that the cost of treatment in Vietnam is lower than some countries in the region and the proportions of the cost components presented in different studies in Vietnam are different. Keywords Direct cost, exacerbation of COPD, E hospital. [1] Ngo Quy Chau, Nguyen Lan Viet, Nguyen Dat Anh, Pham Quang Vinh, Internal Pathology, Medical Publishing House 1 (2018) 42-50 (in Vietnamese).[2] R.A. Pauwels, A.S. Buist, P.M.A. Calverley, C. R. Jenkins, S. Hurd Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 163 (2001) 1256–1276. https://doi.org/10.1164/ajrccm.163.5.2101039[3] https://www.chestnet.org/News/Press-Releases /2014/07/CDC-reports-36-billion-in-annual financial-cost-of-COPD-in-US (15/10/2019)[4] S.D. Sullivan, S.D. Ramsey, T.A. Lee, The economic burden of COPD. Chest 2000 Feb 117(2), 5S-9S.https://journal.chestnet.org/article/S0012-3692(15)52748-7/fulltext[5] Vanfleteren, E.G.W. Lowie, et al Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease American journal of respiratory and critical care medicine 187(7) (2013) 728-735. https://www.atsjournals.org/doi/full/10.1164/rccm.201209-1665oc [6] Doan Quynh Huong Analysis of direct costs of inpatient treatment for EPI in Respiratory Center of Bach Mai Hospital from 2013-2015, 2017 (in Vietnamese).[7] Vu Xuan Phu, Duong Viet Tuan, Nguyen Thu Ha et al., Inpatient treatment costs of patients with chronic obstructive pulmonary disease at central lung hospital, 2009, Journal of Practical Medicine 1 (2012) 51-53 (in Vietnamese).http://yhth.vn/chi-phi-dieu-tri-noi-tru-cua-benh-nhan-benh-phoi-tac-nghen-man-tinh-tai-benh-vien-phoi-trung-uong-nam-2009_t3254.aspx[8] C.S. Rand, M. Nides, M.K. Cowles, R.A. Wise, J. Connett, Long-term metered-dose inhaler adherence in a clinical trial. The lung health study research group. Am J Respir Crit Care Med, Aug 152(2) (1995) 580-8. https://doi.org/10.1164/ajrccm.152.2.7633711[9] Phan Thi Thanh Hoa, Clinical features, clinical and direct treatment costs of patients with chronic obstructive pulmonary disease at Respiratory Center - Bach Mai Hospital Graduation thesis general practitioner, Hanoi Medical University 2013 (in Vietnamese).

FRI0502 SEASONAL CLUSTERING OF ACUTE SARCOIDOSIS IN GERMANY AND ASSOCIATIONS WITH AIR POLLUTION

Background:Sarcoidosis is a multisystemic granulomatous disorder of unknown origin. The central role of macrophages and granuloma formation, the predominant involvement of lung and skin, and certain risk populations (e.g. firefighters1, 2) might be explained by causative airborne antigen(s)3. Whether air pollution is involved in pathogenesis and seasonal clustering of sarcoidosis is uncertain.Objectives:This study has been set to analyze seasonal clustering of acute sarcoidosis and associations to air pollution.Methods:Patients with acute sarcoidosis, defined by bihilar lymphadenopathy, ankle swelling, and/or erythema nodosum plus physician’s diagnosis,were included in this retrospective study. Disease onset (seasonal clustering) and associations to air pollution (particulate matter (PM10) and nitrogen dixoide (NO2)) were analyzed. Google Trends queries were conducted to address seasonal clustering on a global scale.Results:A total of 185 patients with acute sarcoidosis were included; 48.7 % of the enrolled patients were female and Löfgren triad was complete in 73.5 % of patients. Acute sarcoidosis clustered from December to June in West Germany (p<0.005, Kendall τ=-0.68), peaking in January (17.8 % of cases) and in the first third of the year (54.5 %). Mean PM10values clustered from December to April with values between 15 and 40 µg/m3. NO2levels were measured highest from November to March (45 µg/m3) and lowest between April and August (25 µg/m3). Elevated air pollution markers (PM10and NO2) were associated with higher monthly incidence rates of acute sarcoidosis (Cross correlation coefficient ranging between 0.7 -0.8). Google Trends analysis yielded seasonal clustering (p<0.005, Kendall τ = -0.64) in winter and spring months on the northern hemisphere.Conclusion:In Central Europe acute sarcoidosis peaks in winter and spring months (December until March) shortly after PM10and NO2maxima are reached. Whether components of particulate matter might be involved in the pathogenesis of sarcoidosis has to be elucidated by further studies.References:[1] Prezant DJ, Dhala A, Goldstein A, Janus D, Ortiz F, Aldrich TK, et al. The incidence, prevalence, and severity of sarcoidosis in New York City firefighters. Chest. 1999;[2] Webber MP, Yip J, Zeig-Owens R, Moir W, Ungprasert P, Crowson CS, et al. Post-9/11 sarcoidosis in WTC-exposed firefighters and emergency medical service workers. Respir Med [Internet]. 2017;132:232–7.[3] Newman LS, Rose CS, Bresnitz EA, Rossman MD, Barnard J, Frederick M, et al. A case control etiologic study of sarcoidosis: Environmental and occupational risk factors. Am J Respir Crit Care Med. 2004;170(12):1324–30.Disclosure of Interests:Philipp Rustler: None declared, Dirk Schindler: None declared, Reinhard Voll: None declared, Florian Kollert Employee of: Novartis

Bronchiectasis in patients with chronic obstructive pulmonary disease in a tertiary care center in North-East India

Background: Bronchiectasis is common in patients with Chronic Obstructive Pulmonary Disease (COPD). COPD with bronchiectasis has been considered a phenotype with worse lung function and more severe exacerbations. There is scarce literature on the characteristics and optimal management of such patients.Methods:Patients with COPD reporting within the one-year study period were subjected to High Resolution Computed Tomography (HRCT) scan of the thorax. Sputum was sent for Gram-stain and culture/sensitivity for patients found to have bronchiectasis. Bronchiectasis Severity Index (BSI) was calculated using the online BSI calculator. Association between presence of bronchiectasis and gender, lung function and frequency of exacerbations was statistically analysed.Results: Total 62 patients with COPD were enrolled. Bronchiectasis was present in 11 (17.7%) patients. The most common bacterial isolate from sputum of patients with bronchiectasis was Haemophilus influenza (54.54%). The prevalence of bronchiectasis was more in females (19.45% compared to 15.4% in males), but this association was not found to be statistically significant(p=0.748). Forced Expiratory volume in 1st second (FEV1) was found to be significantly lower in patients with bronchiectasis (p<0.05). There was increased frequency of exacerbations among patients with bronchiectasis. This association was however not found to be statistically significant (p=0.765), 1 (9.1%) patient had low BSI score (0-4), 3 (27.3%) patients had intermediate BSI score (5-8) and 7 (63.3%) patients had high BSI score (≥9).Conclusions:The presence of bronchiectasis in COPD is a phenotype associated with a poor clinical course. The characteristics of this co-existence are largely unknown. More studies are required to properly characterize and manage patients with this coexistence. 1. Global Initiative for Chronic Obstructive Lung Disease Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2014. Available at: http://wwwgoldcopdorg/. Accessed 1 February, 20182. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2019 report. Available at: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed 24 January 2019.3. Martínez-García MA, de la Rosa Carrillo D, Soler-Cataluña JJ, Donat-Sanz Y, Serra PC, Lerma MA, et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respirat Crit Care Med. 2013 Apr 15;187(8):823-31.4. Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CFbronchiectasis. Thorax. 2010 Jul 1;65(Suppl 1):i1-58.5. Mao B, Lu HW, Li MH, Fan LC, Yang JW, Miao XY, et al. The existence of bronchiectasis predicts worse prognosis in patients with COPD. Scientific reports. 2015 Jun 16;5:10961.6. Jin J, Yu W, Li S, Lu L, Liu X, Sun Y. Factors associated with bronchiectasis in patients with moderate-severe chronic obstructive pulmonary disease. Med (Baltimore) 2016;95(29):e4219.7. Du Q, Jin J, Liu X, Sun Y. Bronchiectasis as a co morbidity of chronic obstructive pulmonary disease: a systematic review and meta-analysis. PLoS One. 2016;11(3):e0150532.8. Ni Y, Shi G, Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with co morbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015;10:1465-75.9. Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj A, Meister M, et al. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J. 2009;34(4):843-9.10. Rakhimova E, Wiehlmann L, Brauer AL, Sethi S, Murphy TF, Tummler B. Pseudomonas aeruginosa population biology in chronic obstructive pulmonary disease. J Infect Dis. 2009;200(12):1928-35.11. Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, et al. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014;189(5):576-85.12. Dou S, Zheng C, Cui L, Xie M, Wang W, Tian H, et al. High prevalence of bronchiectasis in emphysema-predominant COPD patients. Int J Chron Obstruct Pulmon Dis. 2018;13:2041-7.13. Ramakrishna R, Ambica A. Association of Bronchiectasis in Moderate to Severe COPD patients attending Katuri Medical College Hospital, Guntur from 2011-2013. J Evidence Based Med Healthcare 2015;2(13):2062-76.14. Martinez-Garcia MA, Soler-Cataluna JJ, Donat Sanz Y, Catalan Sera P, Agramunt Lerma M, Ballestin Vicente J, et al. Factors associated with bronchiectasis in patients with COPD. Chest 2011;140(5):1130-7.15. Kumar S, Singh GV, Gupta RK, Singh H, Prakash G. To estimate the prevalence of bronchiectasis in COPD patients. IOSR JDMS. 2018;17(3):82-90.16. Woodhead M, Blasi F, Ewig S. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J. 2005;26:1138-80.17. Patel IS, Vlahos I, Wilkinson TM, Lloyd-Owen SJ, Donaldson GC, Walks M, et al. Bronchiectasis, Exacerbation indices and Inflammation in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2004;170(4):400-7.18. Chen YH, Sun YC. Bronchiectasis as a co morbidity of chronic obstructive pulmonary disease: implications and future research. Chin Med J (Engl). 2016;129(17):2017-9.19. Gatheral T, Kumar N, Sansom B. COPD-related bronchiectasis; independent impact on disease course and outcomes. COPD. 2014;11(6):605-14.20. Goeminne PC, Nawrot TS, Ruttens D, Seys S, Dupont LJ. Mortality in non-cystic fibrosis bronchiectasis: a prospective cohort analysis. Respir Med. 2014 Feb 1;108(2):287-96.21. Hurst JR, Elborn JS, De Soyza A. COPD–bronchiectasis overlap syndrome. Eur Respir J. 2015;45:310-3.

mSphere of Influence: Adenosine in Host Defense against Bacterial Pneumonia—Friend or Foe?

ABSTRACT Elsa N. Bou Ghanem works in the field of innate immune senescence, inflammation, and host defense. In this mSphere of Influence article, she reflects on how “Adenosine A2B receptor deficiency promotes host defenses against Gram-negative bacterial pneumonia” by Barletta et al. (K. E. Barletta, R. E. Cagnina, M. D. Burdick, J. Linden, and B. Mehrad, Am J Respir Crit Care Med 186:1044–1050, 2012, https://doi.org/10.1164/rccm.201204-0622OC) impacted her own work examining the role of the extracellular adenosine pathway in neutrophil responses and host defense against pneumococcal pneumonia.

Roflumilast does not decrease COPD exacerbations in adequately treated patients, but subgroup analysis allows for shared decision making

<p>A critical appraisal and clinical application of Martinez FJ, Rabe KF, Sethi S, et al. Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting beta2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE(2)SPOND). A Randomized Clinical Trial. <em>Am J Respir Crit Care Med</em>. Sep 1 2016;194(5):559-567. doi: <a href="https://doi.org/10.1164/rccm.201607-1349OC">10.1164/rccm.201607-1349OC</a>.</p>