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Background Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Background and Objective: Postinfectious bronchiolitis obliterans (PIBO) is an uncommon and severe form of chronic obstructive lung disease in children. Adenovirus (ADV) is the main pathogen of PIBO in children. However, the risk factors of ADV-PIBO are not fully understood. This study aims to analyze the clinical characteristics of PIBO caused by ADV and compared with non-ADV-PIBO. Materials and Methods: A retrospective study of children under the age of 14 years diagnosed PIBO was performed in 56 ADV-PIBO cases, 29 non-ADV-PIBO, and 39 healthy controls to determine clinical characteristics of PIBO. Results: There was no difference between ADV-PIBO and non-ADV-PIBO cases in gender, age, individual and family atopy or history of asthma, and previous history of wheezing and no difference in the clinical manifestations and signs between the two groups. However, the hospital stay, duration of ventilator use, and multifocal pneumonia incidence of ADV-PIBO group have a significant differences compared with non-ADV-PIBO. Notably, inflammatory markers lactic dehydrogenase (LDH), interleukin 8 (IL-8), and interferon-gamma (IFN-γ) were significantly increased in PIBO patients, and those expressed in ADV-PIBO patients were higher than those in non-ADV-PIBO patients. In addition, ADV-PIBO children required a longer duration of oral prednisone and azithromycin than non-ADV-PIBO cases. Conclusions: Compared with non-ADV-PIBO, ADV-PIBO has a longer hospital stay, longer duration of ventilator use, increased LDH, IL-8, and IFN-γ expressions, and longer duration of oral prednisone and azithromycin treatment. Further research is needed to determine why PIBO caused by ADVs are more severe than those caused by other pathogens.

Background The treatment with short-acting beta-2 agonists (SABA) alone is no longer recommended due to safety issues. Instead, the current Global Initiative for Asthma (GINA) Report recommends the use of the combination of inhaled corticosteroids (ICS) with the rapid/long-acting beta-2 agonist formoterol, although the use in steps 1 and 2 is still off-label in the EU and in many countries. It is important to understand clinicians’ knowledge and opinions on the issue with the ultimate goal to encourage the implementation of the new approach in clinical practice. Methods We performed an international survey, directed to pulmonologists interested in the management of patients with asthma. Results Most participants reported that SABA alone should not be used in GINA Step 1 asthma treatment. As-needed low-dose ICS/formoterol combination to patients in step 1, and as-needed low-dose ICS/formoterol as reliever therapy in any step were found to be of current use prescribed in their real-life settings. SABA alone was still prescribed to a proportion of patients, although the pulmonologists’ opinion was that it should no longer be used. Conclusions Most specialists are up to date and understand the relevance of the changes in GINA reports from 2019. Nevertheless, dissemination and implementation of GINA novel management strategy is still needed.

Background When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. Methods Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. Results We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. Conclusion We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.

PURPOSE: This study aims to investigate whether there is a significant difference between typical and atypical parenchymal patterns in the development of fibrosis, which is the most crucial factor affecting morbidity in pulmonary sarcoidosis. METHODS: In our hospital, 145 cases with Siltzbach Types 2 and 3 sarcoidoses diagnosed by clinical, radiological, and histopathologic were retrospectively investigated. Perilymphatic nodules, accompanying mosaic attenuation, and interlobular septal thickening and central peribronchovascular bunch-like thickening on high-resolution computed tomography were assessed as typical. Solid nodules, galaxy finding, consolidation, ground-glass opacity, isolated mosaic attenuation, and interlobular septal thickening, and pleural fluid were accepted as atypical findings. Findings indicating fibrosis were fine and rough reticular opacity, traction bronchiectasis, volume loss, and cystic changes. For the analysis of variables, SPSS 25.0 program was used. RESULTS: Ten (16%) of the 61 cases with typical findings and 16 (19%) of the 84 with atypical findings developed fibrosis (P = 0.827). The mean age of cases with fibrosis was higher. With the cut-off of 50 years, sensitivity was 61.5%, and specificity was 68.9%. The highest fibrosis rate was in cases with ground glass pattern (n = 7/17), whereas higher reversibility rates were in those with miliary pattern (n = 9/12) and galaxy sign (n = 5/6). CONCLUSION: The incidence of fibrosis is higher in the atypical group with no significant difference. The incidence of fibrosis differs in each atypical pattern, being highest in ground-glass opacity and lowest in the miliary pattern.

Background It is important to identify deterioration in normotensive patients with acute pulmonary embolism (PE). This study aimed to develop a tool for predicting deterioration among normotensive patients with acute PE on admission. Methods Clinical, laboratory, and computed tomography parameters were retrospectively collected for normotensive patients with acute PE who were treated at a Chinese center from January 2011 to May 2020 on admission into the hospital. The endpoint of the deterioration was any adverse outcome within 30 days. Eligible patients were randomized 2:1 to derivation and validation cohorts, and a nomogram was developed and validated by the aforementioned cohorts, respectively. The areas under the curves (AUCs) with 95% confidence intervals (CIs) were calculated. A risk-scoring tool for predicting deterioration was applied as a web-based calculator. Results The 845 eligible patients (420 men, 425 women) had an average age of 60.05 ± 15.43 years. Adverse outcomes were identified for 81 patients (9.6%). The nomogram for adverse outcomes included heart rate, systolic pressure, N-terminal-pro brain natriuretic peptide, and ventricle/atrial diameter ratios at 4-chamber view, which provided AUC values of 0.925 in the derivation cohort (95% CI 0.900–0.946, p p https://gaoyzcmu.shinyapps.io/APE9AD/). Conclusions We developed a web-based scoring tool that may help predict deterioration in normotensive patients with acute PE.

Context: Percutaneous needle biopsy of lung (PCNBL) is advantageous over bronchoscopic biopsies to obtain adequate sample for peripheral lung lesions. Objective: The objective was to evaluate the diagnostic yield of image-guided PCNBL in the diagnosis of lung lesions and to classify lung carcinomas as per the recently proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society/European Respiratory Society classification for small biopsies modified and adopted by the World Health Organization, 2015. Materials and Methods: A total of 280 image-guided PCNBL were analyzed. The radiological findings and routine hematoxylin and eosin (H&E)-stained sections along with immunohistochemistry (IHC) were analyzed in all the cases. Molecular testing was done depending on tissue diagnosis and availability. Results: Majority (81%) were diagnosed as malignant lesions, with adenocarcinoma (ADC) being the most common. More than 70% were diagnosed on H&E morphology alone, with thirty cases requiring IHC to categorize as ADC. Nearly 60% were categorized as squamous cell carcinoma on morphology alone and the rest required IHC. Though TTF1 showed higher sensitivity than napsin A, the latter is more specific. Both p63 and p40 were found to be highly sensitive for squamous cell carcinoma, but p40 was more specific than p63. Epidermal growth factor receptor could be evaluated on 94.4% of ADC samples, indicating good yield for molecular testing. Conclusion: PCNBL yields adequate sampling for tissue diagnosis and ancillary testing with minimal complications. The use of IHC markers reduces the number of non-small-cell not otherwise specified cases significantly.

Background There is only limited clinical data on the benefit of intense immunosuppression in patients with severe interstitial pneumonia associated with autoimmune features or new-onset connective tissue disease. Case presentation We here report a series of three consecutive patients suffering from severe interstitial lung disease necessitating endotracheal intubation and mechanical ventilation. The first two patients fulfilled many diagnostic criteria for new-onset antisynthetase syndrome, the third patient for systemic lupus erythematosus. We decided to implement aggressive immunosuppressive strategies in these critically-ill patients including therapeutic plasma exchange, immunoadsorption, cyclophosphamide and rituximab. All three patients improved from respiratory failure, were successfully weaned from the respirator, and eventually dismissed from hospital with ongoing immunosuppressive therapy. Conclusion Patients suffering from severe connective tissue disease-associated interstitial lung disease and respiratory failure may benefit from an aggressive immunosuppressive regimen and extracorporeal blood purification with rapid reduction of circulating autoantibodies. The impressive clinical responses in this small case series warrant a controlled clinical trial.

One of the idiopathic respiratory tract inflammation is cryptogenic organizing pneumonia (COP). Most patients are symptomatic for

Background and objectives Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. Methods This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). Results Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. Conclusions The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

Pulmonary artery sarcoma (PAS) is a rare and devastating disease. The diagnosis is often delayed, and optimal treatment remains unclear. The aim of this study is to report our experience in the surgical management of this disease. Between 2000 and 2018, 17 patients underwent operations for PAS at our center. The medical records were retrospectively reviewed to evaluate the clinical characteristics, operative findings, the postoperative outcomes, and the long-term results. The mean age at operation was 46.0 ± 12.4 years (range, 26–79 years), and eight (47.1%) patients were male. Six patients underwent tumor resection alone, whereas the other 11 patients received pulmonary endarterectomy (PEA). There were two perioperative deaths. Follow-up was completed for all patients with a mean duration of 23.5 ± 17.6 months (1–52 months). For all 17 patients, the median postoperative survival was 36 months, and estimated cumulative survival rates at 1, 2, 3, and 4 years were 60.0%, 51.4%, 42.9%, and 21.4%, respectively. The mean survival was 37.0 months after PEA and 14.6 months after tumor resection only ( p = 0.046). Patients who had no pulmonary hypertension (PH) postoperatively were associated with improved median survival (48 vs. 5 months, p = 0.023). In conclusion, PAS is often mistaken for chronic pulmonary thromboembolism. The prognosis of this very infrequent disease remains poor. Early detection is essential for prompt and best surgical approach, superior to tumor resection alone, and PEA surgery with PH relieved can provide better chance of survival.

The COVID-19 pandemic has awakened the need for telemedicine and teleconsultation to continue medical care while maintaining social distancing for safety against infection. The concept of the electronic intensive care unit (e-ICU) is evolving rapidly in developed nations. e-ICU in developing countries like India not only has great potential but also has many roadblocks. This article showcases the concept, advantages, and challenges of e-ICU in India, with a glimpse of the future.

Introduction Trust and satisfaction play vital roles in how smokers react to smoking cessation treatment delivered by physicians. This paper aims to ascertain whether smoking status and pack-years of smoking affect trust in physicians and satisfaction with the health system in China. Methods The current study used the ordered probit model to evaluate how smoking status affects trust in physicians and satisfaction with the health system in China. Data from the China Family Panel Studies (CFPS) 2018 were used for the analysis, and the final sample consisted of 29500 adults. The CFPS is a nationally representative, comprehensive, high-quality, biennial longitudinal survey of Chinese communities, families, and individuals. The survey was conducted in 25 provinces and their administrative equivalents. The population of 25 provinces represents 95% of the total population in Mainland China. Results According to the ordered probit model, the results showed that current smokers were significantly negatively associated with trust in physicians, and more cigarette smoking was associated with decreased trust in physicians. Moreover, current smokers were also significantly negatively related to satisfaction with the health system. Conclusions The present study found that current smokers would be more likely to rate trust in physicians lower, and less likely to rate greater satisfaction with the health system, than never smokers. These results may have important implications for regaining trust in physicians from smokers and supporting health-system reform for tobacco treatment.

Background: The deadly outbreak of coronavirus disease 2019 (COVID-19) has imposed many challenges to health-care professionals (HCPs). The knowledge, confidence in performing clinical skills, and psychological impact have been studied among various HCP. Respiratory therapists (RTs) are the frontliners in handling critically ill COVID-19 victims. Although being an integral part, there are no studies on RTs in COVID-19. Hence, we aim to study the knowledge, confidence, and perception of RTs in managing COVID-19. Subjects and Methods: A cross-sectional, questionnaire-based survey conducted among RTs in India. The present study was conducted from July 15, 2020, to August 1, 2020. Descriptive analysis was used to describe demographics, mean knowledge, confidence levels, perception, and psychological impact on RTs. Results: A total of 68 RTs responded with a response rate of 70.8%. Of them, 60% (41) had good knowledge, 96% (65) had higher confidence in performing required clinical skills, 98.5% (67) had a perception that RTs plays an essential role in COVID-19 care, and 98.5% (67) had a negative psychological impact. Reliability of the questionnaire was found to be in acceptable range. Conclusions: This study found that RTs in general had good knowledge and higher level confidence in performing procedure related to COVID-19. RTs perceive that the role of RT in COVID-19 is important.

Damian Chi Hong Siu,1,2 Chi Tao So,1,3 Cherry Wai Lee Lau,1,4 Eric Hei Man Hui,1,5 Alexandra Fung,1,6 Tak Ming Chan,1,7 Fion Siu Fun Chan,1,3 Catherine Kam Fung Chan,1,8 William Pang Wai Chen,1,9 Sammy Hoo Ming Cheung,1,10 Katherine Pui Yee Chan,1,11 Peter Poon,12 Michael Cheung,12 Cherry Chan,12 Justin Tse,12 Vanessa Fung,12 Kenneth NK Fong12 1Respiratory Sub-Specialty Group, Occupational Therapy Central Organization Committee, Hospital Authority, Hong Kong SAR; 2Occupational Therapy Department, Prince of Wales Hospital, Hospital Authority, Hong Kong SAR; 3Occupational Therapy Department, Princess Margaret Hospital, Hospital Authority, Hong Kong SAR; 4Occupational Therapy Department, Kowloon Hospital, Hospital Authority, Hong Kong SAR; 5Occupational Therapy Department, Grantham Hospital, Hospital Authority, Hong Kong SAR; 6Occupational Therapy Department, Ruttonjee Hospital, Hospital Authority, Hong Kong SAR; 7Occupational Therapy Department, Haven of Hope Hospital, Hospital Authority, Hong Kong SAR; 8Occupational Therapy Department, Wong Tai Sin Hospital, Hospital Authority, Hong Kong SAR; 9Occupational Therapy Department, Tseung Kwan O Hospital, Hospital Authority, Hong Kong SAR; 10Occupational Therapy Department, Tuen Mun Hospital, Hospital Authority, Hong Kong SAR; 11Occupational Therapy Department, Alice Ho Miu Ling Nethersole Hospital, Hospital Authority, Hong Kong SAR; 12Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SARCorrespondence: Damian Chi Hong SiuOccupational Therapy Department, Hospital Authority, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong SAR Email damiansiu@gmail.comBackground: The Manchester Respiratory Activities of Daily Living Questionnaire (MRADLQ) is a valid and reliable tool measuring the functional level of patients with COPD in multidimensional aspects. However, a local validation of the questionnaire is lacking in Hong Kong.Objective: To develop a Chinese version of MRADLQ with pictorial enhancement (C-MRADLQ) and study its reliability and validity.Patients and Methods: A total of 238 patients suffering from COPD were recruited from nine public hospitals and five Nurse and Allied Health Respiratory Clinics by convenient sampling. A total of 64 patients with normal spirometry results and no previous clinical diagnosis of COPD were invited to complete the C-MRADLQ for comparison and examination of its validity. Ten out of 302 patients were re-assessed with the C-MRADLQ after one week by the same rater for test–retest reliability. The C-MRADLQ was correlated with spirometry result, COPD classifications and groups by Global Initiative for Chronic Obstructive Lung Disease (GOLD), the modified Medical Research Council Dyspnea Scale (mMRC Dyspnea Scale), COPD Assessment Test (CAT), Chinese Version of the Shortness of Breath Questionnaire (C-SOBQ), number of admission and the ADO index.Results: The C-MRADLQ shows good test–retest reliability as indicated by an intra-class correlation coefficient value of 0.975. It is significantly correlated with COPD stage, COPD group, SOBQ score, CAT score, mMRC, ADO index, spirometry results, and number of admissions. The SOBQ score, number of admissions, FEV1/FVC, and COPD group could significantly predict the total C-MRADLQ score. A total of 67.9% of participants’ mMRC levels were correctly classified by using the C-MRADLQ total score. The agreement of the original and new versions of questions 20 and 21 of C-MRADLQ was 97.3% and 90.1%, respectively.Conclusion: The pictorial version of the C-MRADLQ is a validated and reliable functional assessment tool to measure functional status among patients with COPD in the Chinese population.Keywords: pulmonary disease, chronic obstructive, patient-reported outcome measures, activities of daily living, validation study, occupational therapy

Introduction Invasive mechanical ventilation (IMV) is associated with several complications. Placement of a long-term airway (tracheostomy) is also associated with short and long-term risks for patients. Nevertheless, tracheostomies are placed to help reduce the duration of IMV, facilitate weaning and eventually undergo successful decannulation. Methods We performed a narrative review by searching PubMed, Embase and Medline databases to identify relevant citations using the search terms (with synonyms and closely related words) “non-invasive ventilation”, “tracheostomy” and “weaning”. We identified 13 publications comprising retrospective or prospective studies in which non-invasive ventilation (NIV) was one of the strategies used during weaning from IMV and/or tracheostomy decannulation. Results In some studies, patients with tracheostomies represented a subgroup of patients on IMV. Most of the studies involved patients with underlying cardiopulmonary comorbidities and conditions, and primarily involved specialized weaning centres. Not all studies provided data on decannulation, although those which did, report high success rates for weaning and decannulation when using NIV as an adjunct to weaning patient off ventilatory support. However, a significant percentage of patients still needed home NIV after discharge. Conclusions The review supports a potential role for NIV in weaning patients with a tracheostomy either off the ventilator and/or with its decannulation. Additional research is needed to develop weaning protocols and better characterize the role of NIV during weaning.

Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects, like pneumonitis, can be life-threatening. Pneumonitis is caused by direct cytotoxic effect, oxidative stress, and immune-mediated injury. Radiotherapy Induced Lung Injury (RILI) encompasses two phases: an early phase known as Radiation Pneumonitis (RP), characterized by acute lung tissue inflammation as a result of exposure to radiation; and a late phase called Radiation Fibrosis (RF), a clinical syndrome that results from chronic pulmonary tissue damage. Currently, diagnoses are made by exclusion using clinical assessment and radiological findings. Pulmonary function tests have constituted a significant step in evaluating lung function status during radiotherapy and useful predictive tools to avoid complications or limit toxicity. Systemic corticosteroids are widely used to treat pneumonitis complications, but its use must be standardized, and consider in the prophylaxis setting given the fatal outcome of this adverse event. This review aims to discuss the clinicopathological features of pneumonitis and provide practical clinical recommendations for prevention, diagnosis, and management.

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused ( n = 49) or normally perfused group ( n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score −0.793 , R 2 = 0.225, p

Background Extranodal natural killer/T cell lymphoma (ENKL) is a rare subtype of non-Hodgkin lymphoma, and lung involvement is extremely rare. The patients with pulmonary ENKL always presented unspecific symptoms of the respiratory system, such as cough with sputum and varying degrees of fever, while developing into acute respiratory distress (ARDS) was seldomly reported, especially promoted by the surgical procedure. Case presentation Here we describe a patient with nasal ENKL and most likely lung dissemination that was regarded as an infection at first. After nonresponse to a period of anti-infective therapy, this patient received surgical debridement. While the histopathology did not show the evidence of infection, but consistent with ENKL. The patient got refractory hypoxemia rapidly after surgery, with the LDH surging to a much higher level than before surgery. The ARDS was diagnosed, and he died on the 5th day after surgery. We postulate that ARDS was due to aggressive lymphoma proliferation promoted by the surgical procedure. Conclusions Pulmonary ENKL developing into ARDS was scarce, and was likely attributed to the aggressive tumor cell proliferation after surgery in this case.

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low-, moderate-, and high-load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low-load (25 W) exercise was significantly lower in men, although that at maximum-load exercise was not different between men and women. In the Kaplan–Meier analysis, in a median follow-up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low-load exercise showed poorer survival ( P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low-load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low-load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.

Benjamin D Horne,1,2 Rehan Ali,3 Dawn Midwinter,3 Catherine Scott-Wilson,4 Courtney Crim,4 Bruce E Miller,5 David B Rubin4 1Intermountain Medical Center Heart Institute, Salt Lake City, UT, USA; 2Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA; 3GlaxoSmithKline Plc., Uxbridge, UK; 4GlaxoSmithKline Plc., Research Triangle Park, Raleigh, NC, USA; 5GlaxoSmithKline Plc., Collegeville, PA, USACorrespondence: Benjamin D HorneIntermountain Medical Center Heart Institute, 5121 S Cottonwood Street, Salt Lake City, UT 84107, USAEmail benjamin.horne@imail.orgIntroduction: The presence of cardiovascular (CV) risk factors and CV disease in patients with chronic obstructive pulmonary disease (COPD) leads to worse outcomes. A number of tools are currently available to stratify the risk of adverse outcomes in these patients with COPD. This post hoc analysis evaluated the Summit Lab Score for validation as a predictor of the first episode of moderate-to-severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and other outcomes, in patients with COPD and high arterial pulse wave velocity (aPWV).Methods: Data from a multicenter, randomized, placebo-controlled, double-blind study were retrospectively analyzed to evaluate treatment effects of once-daily fluticasone furoate/vilanterol 100/25 μg in patients with COPD and an elevated CV risk (aPWV≥ 11m/s) over 24 weeks. The previously derived Summit Lab Score and, secondarily, the Intermountain Risk Score (IMRS) were computed for each patient, with patients then stratified into tertiles for each score. Risk of moderate-to-severe AECOPD was analyzed across tertiles using Kaplan–Meier survival curve and Cox regression analyses.Results: In 430 patients with COPD, Kaplan–Meier probabilities of no moderate-to-severe AECOPD for Summit Lab Score tertiles 1, 2, and 3 were 92.3%, 95.5%, and 85.1%, respectively (P trend = 0.015), over 24 weeks. Grouped by IMRS tertiles, the respective probabilities were 92.9%, 91.2%, and 88.3%, respectively (P trend = 0.141). Length of stay in the hospital (P = 0.034) and the hospital ward (P = 0.042) were also significantly different between Summit Lab Score tertiles but not for intensive care (P = 0.191).Conclusion: The Summit Lab Score was associated with the 24-week risk of moderate-to-severe AECOPD in COPD patients with elevated CV risk. Secondarily, IMRS showed a trend towards differences in the risk of AECOPD, which was not statistically significant.Keywords: chronic obstructive pulmonary disease (COPD), risk assessment, cardiovascular (CV) risk, arterial stiffness, Summit Lab Score, Intermountain Risk Score (IMRS)

Computer-based quantitative computed tomography analysis has a growing role in the clinical evaluation, prognosis, and longitudinal management of diffuse parenchymal diseases. It provides improved characterization and quantification of disease. The pulmonary vessel-related structure score is a purely computer-based parameter that cannot be evaluated by the human eye and allows us to prognosticate outcomes in patients with fibrosing interstitial lung disease.

Background Clinical management of COVID-19 requires close monitoring of lung function. While computed tomography (CT) offers ideal way to identify the phenotypes, it cannot monitor the patient response to therapeutic interventions. We present a case of ventilation management for a COVID-19 patient where electrical impedance tomography (EIT) was used to personalize care. Case presentation The patient developed acute respiratory distress syndrome, required invasive mechanical ventilation, and was subsequently weaned. EIT was used multiple times: to titrate the positive end-expiratory pressure, understand the influence of body position, and guide the support levels during weaning and after extubation. We show how EIT provides bedside monitoring of the patient´s response to various therapeutic interventions and helps guide treatments. Conclusion EIT provides unique information that may help the ventilation management in the pandemic of COVID-19.

Background: E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of nonsmokers or combustible cigarette smokers in Korea. Methods: In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013-2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). Results: Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than nonsmokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p

Bronchoscopy is an extremely useful diagnostic and therapeutic procedure that finds an invaluable place in Pulmonology practice. Due to aerosol generation, bronchoscopy carries a high risk of infection transmission to health care workers and other patients. This fact is even more important in the present times of COVID-19 pandemic owing to its droplet- (and possibly aerosol-) mediated spread. With this background, a working group extracted literature through electronic search of PubMed and Google Scholar databases. All relevant documents were comprehensively reviewed and consensus recommendations formulated based on the level of available evidence. Where evidence was insufficient, Usual Practice Points were formulated based on expert opinion. This resultant document attempts to present clinical recommendations for performing flexible bronchoscopy in COVID-19 suspect/confirmed patients. It outlines important general considerations for bronchoscopy in these cases, provides an algorithmic approach to patient selection for bronchoscopy during these extraordinary times, and enlists critical do's and don'ts that should be followed before, during, and after the procedure. To conclude, flexible bronchoscopy must be cautiously performed amid the COVID-19 crisis. Judicious case selection and meticulous contact and airborne precautions are important to minimise infection transmission.

Inhalational route is the cornerstone for drug delivery in asthma. Dry powder inhalers efficiently deliver drug particles to lungs depending on patients' breath actuation and without using propellants. Drug delivery in lungs is dependent primarily on particle size distribution of the formulation. Several studies have proved that drug particles 1–3 μm in size provide optimum efficacy with minimum adverse events. Particles >3 μm are deposited in the oropharynx and those

Background A positive D-dimer test has high sensitivity but relatively poor specificity for the diagnosis of pulmonary embolism, causing difficulty for clinicians unskilled in pulmonary embolism diagnosis in determining whether a patient with a positive D-dimer test needs to undergo computed tomographic pulmonary angiography. Objectives We sought to develop a new clinical decision-making rule based on a positive D-dimer result to predict the probability of pulmonary embolism and to guide clinicians in making decisions regarding the need for computed tomographic pulmonary angiography. Methods We conducted a prospective, multicenter study in three hospitals in China. A total of 3014 inpatients with positive D-dimer results were included. In the derivation group, we built a multivariate logistic regression model and deduced a regression equation from which our score was derived. Finally, we validated the score in an independent cohort. Results Our score included nine variables (points): chest pain (1.4), chest tightness (2.3), shortness of breath (3.6), hemoptysis (3.4), heart rate ≥100 beats/min (3.6), blood gas analysis (2.9), electrocardiogram presenting a typical S1Q3T3 pattern (4.1), electrocardiogram findings (2.4), and ultrasonic cardiogram findings (3.7). The sensitivities and specificities were 100% and 86.94%, respectively, in the derivation group and 100% and 90.82%, respectively, in the validation group. Additionally, the observed and predicted proportions of patients who underwent computed tomographic pulmonary angiography were 16.82% and 10.76%, respectively, in the derivation group and 18.72% and 11.40%, respectively, in the validation group. Conclusions The new score can categorize inpatients with a positive D-dimer test as pulmonary embolism-likely or pulmonary embolism-unlikely, thus reducing unnecessary computed tomographic pulmonary angiography examinations.

Research question There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. Patients and methods IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated. Results There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ($${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$ 6MWT O 2 group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the $${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$ 6MWT O 2 group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p Conclusion IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.

The coronavirus pandemic, known as coronavirus disease 2019 (COVID-19), is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus first identified in patients from Wuhan, China. Since December 2019, SARS-CoV-2 has spread swiftly around the world, infected more than 25 million people, and caused more than 800,000 deaths in 188 countries. Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) appear to be risk factors for COVID-19, however, their prevalence remains controversial. In fact, studies in China reported lower rates of chronic respiratory conditions in patients with COVID-19 than in the general population, while the trend is reversed in the United States and Europe. Although the underlying molecular mechanisms of a possible interaction between COVID-19 and chronic respiratory diseases remain unknown, some observations can help to elucidate them. Indeed, physiological changes, immune response, or medications used against SARS-CoV-2 may have a greater impact on patients with chronic respiratory conditions already debilitated by chronic inflammation, dyspnea, and the use of immunosuppressant drugs like corticosteroids. In this review, we discuss importance and the impact of COVID-19 on asthma and COPD patients, the possible available treatments, and patient management during the pandemic.

Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p + T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p Conclusions The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

Swyer-James-MacLeod Syndrome (SJMS) is a rare cause of a hyperlucent unilateral hemithorax. It is usually found in childhood and is a long-term sequalae of postinfectious bronchiolitis obliterans. It can be an incidental finding in adults. Most patients are asymptomatic. However, some patients can present with recurrent pulmonary infections, haemoptysis or dyspnoea. The diagnosis of SJMS is made radiographically by chest x-ray and CT scan. Majority of symptomatic patients will require conservative management. It is also important to rule out other diseases which have similar radiological picture as inaccurate diagnoses can lead to inappropriate therapy. Here we report a case of 63-year-old woman who presented with haemoptysis and progressive dyspnoea and was subsequently diagnosed as a case of SJMS.

There is not enough information about short- and long-term complications of coronavirus disease 2019 (COVID-19) infection, following treatment. Pneumothorax due to barotrauma after adult respiratory distress syndrome has been observed in some viral infections. However, spontaneous pneumothorax occurring after treatment is uncommon. We report a case of chronic obstructive pulmonary disease (COPD), who presented to the emergency department with pneumothorax 1 month after receiving treatment for COVID-19 infection. The patient had shortness of breath starting 3 weeks after discharge. He had a history of hospitalization due to a COPD attack within the past year. He was diagnosed as pneumothorax with radiological imaging.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

Luca Richeldi,1 Alessio Piraino,2 Francesco Macagno,1 Gianluigi Micarelli,2 Eleonora Ingrassia2 1Unità Operativa Complessa di Pneumologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico A, Gemelli, Rome; 2Chiesi Italia S.p.a., Parma, ItalyCorrespondence: Gianluigi MicarelliChiesi Italia S.p.a., Via Giacomo Chiesi 1, Parma 43122, ItalyTel +39 345 6350692Fax +39 0521 279592Email g.micarelli@chiesi.comBackground: The fixed triple combination Beclometasone dipropionate/Formoterol fumarate/Glycopyrronium (BDP/FF/G, Trimbow®), an extrafine formulation in a unique pressurized metered dose inhaler, is indicated for the maintenance treatment in adult patients with moderate to severe COPD, not adequately treated by ICS/LABA or LABA/LAMA. Besides the evidence from three randomized controlled trials, the impact of fixed triple therapy has not been extensively evaluated in a real-world population of COPD patients. TRITRIAL (TRIple Therapy in Real life: Impact on Adherence and HeaLth status) is a non-interventional study to assess the effect of BDP/FF/G in a real world setting in Italy.Design: TRITRIAL is a 12-month, multicenter, cohort, prospective, longitudinal observational study. Two follow-up visits will be performed at 6 and 12 months, respectively. The study includes the collection of anamnestic clinical and functional data before the start of BDP/FF/G. The study is built for digital conduction, from signature of the informed consent on a dedicated web platform, to the collection of questionnaires and clinical data on the eCRF.Population: A total of 800 patients with COPD ranging from Global Initiative for Obstructive Lung Disease (GOLD) stages 2 to 4, receiving therapy with BDP/FF/G according to the Summary of Product Characteristics and local clinical practice, will be recruited. All concomitant therapies will be permitted for the duration of the study.Evaluations: The primary endpoint is the change of CAT score at 12 months versus baseline. Secondary endpoints are adherence, health-related quality of life, sleep quality, disease-related outcomes (lung function and COPD exacerbations), device usability, economic resources consumption, and safety.Conclusion: TRITRIAL study is expected to give relevant information about effectiveness of BDP/FF/G fixed triple therapy in a real-life setting of patients with COPD, where adherence, usability of inhalers and patient’s preference of the device are crucial factors for the success of the therapy.Keywords: COPD, symptoms, health status, adherence, LAMA, LABA, ICS

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, novel enveloped RNA beta-coronavirus. The clinical manifestations vary from no symptoms to fever, cough, respiratory distress, pneumonia, and adult respiratory distress syndrome (ARDS) or uncommonly diarrhea. Typically, the disease has viremic phase, pulmonary phase, and severe host inflammatory phase. Prompt interventions in the first two phases such as awake prone positioning and administration of low-dose corticosteroids can prevent the onset of the third phase of the deadly disease. Awake prone positioning and systemic corticosteroids are simple interventions, which can prevent the requirement of mechanical ventilation and also lead to reduction in the inflammatory response and disease severity. We report a case series of six patients who diagnosed with COVID-19 ARDS and were benefitted by awake prone positioning sessions and low-dose systemic corticosteroid therapy.

BackgroundScreening for lung cancer has used chest radiography (CR), low dose computed tomography (LDCT) and sputum cytology (SC). Estimates of the lead time (LT), i.e., the time interval from detection of lung cancer by screening to the development of symptoms, have been derived from longitudinal studies of populations at risk, tumor doubling time (DT), the ratio between its prevalence at the first round of screening and its annual incidence during follow-up, and by probability modeling derived from the results of screening trials.ObjectiveTo review and update the estimates of LT of lung cancer.MethodsA non-systematic search of the literature for estimates of LT and screening trials. Search of the reference sections of the retrieved papers for additional relevant studies. Calculation of LTs derived from these studies.ResultsLT since detection by CR was 0.8–1.1 years if derived from longitudinal studies; 0.6–2.1 years if derived from prevalence / incidence ratios; 0.2 years if derived from the average tumor DT; and 0.2–1.0 if derived from probability modeling. LT since detection by LDCT was 1.1–3.5 if derived from prevalence / incidence ratios; 3.9 if derived from DT; and 0.9 if derived from probability modeling. LT since detection of squamous cell cancer by SC in persons with normal CR was 1.3–1.5 if derived from prevalence/incidence ratios; and 2.1 years if derived from the DT of squamous cell cancer.ConclusionsMost estimates of the LT yield values of 0.2–1.5 years for detection by CR; of 0.9–3.5 years for detection by LDCT; and about 2 years or less for detection of squamous cell cancer by SC in persons with normal CR. The heterogeneity of the screening trials and methods of derivation may account for the variability of LT estimates.

Introduction: Awake fiberoptic intubation (AFOI) is the gold standard for the management of recognized difficult airway. Good airway anesthesia along with sedation is necessary to ensure patient comfort. Aim: The aim of the study was to evaluate topical lignocaine administered by “spray-as-you-go” versus transtracheal injection technique on intubating conditions during AFOI. Patients and Methods: After obtaining written informed consent, 36 patients were randomly allocated to one of two groups: Group T – transtracheal technique and Group S – Spray-as-you-go technique. All patients were sedated with intravenous dexmedetomidine infusion titrated to a Ramsay Sedation Score of 2–3 during AFOI. All patients received oral gargle and nasal packing with lignocaine 2%. Patients in Group T received 2 mL lignocaine 2% intratracheally just prior to beginning fiberscopy. Patients in Group S received 2 mL lignocaine 2% spray over the vocal cords and another 2 mL below the vocal cords during fiberscopy. Tracheal intubation was then performed. Primary outcome measure was a composite score of patient comfort. Secondary measures were intubation and fiberscopy time, adverse effects, and postoperative patient evaluation. Results: The demographic data were comparable. A composite score of 15 unacceptable. Significantly more patients in Group T had optimal composite score compared to Group S. There were no differences between the two groups as regards postintubation score, ease of intubation, and postoperative survey. Conclusion: During awake nasal fiberoptic intubation, in comparison with spray-as-you-go technique, the transtracheal instillation of lignocaine improves patient tolerance and comfort during tracheal intubation and provides better patient satisfaction.

Rina Juel Kaptain,1,2 Tina Helle,1,2 Ann-Helen Patomella,2 Ulla Møller Weinreich,3,4 Anders Kottorp2,5 1Department of Occupational Therapy, University College of Northern Denmark, Aalborg, Denmark; 2Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 3Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 4The Clinical Institute, Aalborg University, Aalborg, Denmark; 5Faculty of Health and Society, Malmö University, Malmö, SwedenCorrespondence: Rina Juel Kaptain Selma Lagerloefs Vej 2, Aalborg 9220, DenmarkTel +4572690928Email rio@ucn.dkPurpose: There have been calls for more knowledge of activities of daily living (ADL) performance in order to address interventions in pulmonary rehabilitation effectively. Everyday technology (ET) has become an integrated dimension of ADL, impacting the ways in which ADL is performed. To improve everyday functioning and quality of life, the use of ADL and ET use needs to be evaluated and addressed effectively in interventions. Therefore, the aim of this study was twofold: 1) to explore the quality of ADL performance, and 2) to investigate the relationship between observation and self-reported ADL performance and ability to use everyday technologies in people living with COPD.Methods: This cross-sectional study involved 84 participants aged 46– 87 years. Participants were recruited through healthcare centres in the Northern Region of Denmark using a convenience sampling procedure. Data were collected using standardized assessments that investigated different ADL perspectives: self-reported ADL tasks and ET use, observed motor and process ability, and need for assistance. Data were analysed and presented using descriptive statistics and Pearson’s correlation coefficient.Results: The most affected ADL tasks were mobility within or outside the home, lower dressing, bathing, pedicuring, cooking, shopping, cleaning and washing clothes. New insights into the quality of ADL performance in people living with COPD were presented in terms of detailed ADL motor skills and ADL process skills, as well as the predicted need for support to function in the community. Moreover, new insights into the relationship between observation and self-reported ADL performance (r=0.546, p< 0.01; r=0.297, p< 0.01) and between ADL performance and self-perceived ability to use ET (r=0.524, p< 0.01; r=0.273, p< 0.05; r=0.044, p=0.692) were presented.Conclusion: Overall, the knowledge from the present study is valuable for focusing interventions that address challenging ADL performance and ET use through relevant and realistic activities. The ability to use ET is important to evaluate and target pulmonary rehabilitation.Keywords: ADL skills, AMPS, everyday technology, occupational therapy, pulmonary rehabilitation

Adenocarcinoma of lung remains the commonest subtype of lung cancer. Despite of recent advances, the presentation of carcinoma of lung is delayed many of the times until later stages. Here is a case of a young pregnant female with adenocarcinoma of lung with brain metastasis with unusual presentation.

Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

Tze Pin Ng,1 Qi Gao,1 Xinyi Gwee,1 Denise QL Chua,1 Wan C Tan2 1Gerontology Research Programme, Department of Psychological Medicine, National University of Singapore, Singapore; 2Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Tze Pin NgGerontology Research Programme, Department of Psychological Medicine, National University of Singapore, NUHS Tower Block, 9 th Floor, 1E Kent Ridge Road, 119228, SingaporeTel +65-67723478Fax +65-67772191 Email pcmngtp@nus.edu.sgObjective: The anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk. We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥ 55.Methods: GOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC < 0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later.Results: Prevalent cases of COPD consumed less tea than their non-COPD counterparts. Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥ 3 cups/day (OR=0.77, 95% CI=0.61– 0.96). The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17– 0.69) with consuming ≥ 3 cups/day after co-variate adjustment.Conclusion: Different kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea. Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.Keywords: phytochemical, polyphenols, theophylline, epidemiological, longitudinal

Metabolic syndrome is characterized by insulin resistance/hyperinsulinemia, atherogenic dyslipidemia (elevated triglycerides, low HDL), and hyperglycemia. The high prevalence of metabolic syndrome in pulmonary hypertension leads to the hypothesis that metabolic syndrome may play a contributing role in pulmonary hypertension and heart failure with preserved ejection fraction pathogenesis. We present a 62-year-old woman with morbid obesity, mild pre-capillary pulmonary hypertension, and metabolic syndrome. Her metabolic syndrome was treated with a medically-supervised ketogenic diet delivered by a telehealth healthcare team via a continuous remote care platform. Following one year of treatment, metabolic syndrome was reversed, leading to successful weight loss concurrent with hemodynamic improvement. This case highlights the feasibility of using a nutritional strategy to treat pulmonary hypertension associated with obesity and metabolic syndrome, common contributors to group 2 and 3 pulmonary hypertension. We bring this case and technique to the pulmonary hypertension community to share a tool in our therapeutic toolkit and highlight the importance of nutritional advice extending beyond telling a patient they should lose weight to invoking a rational strategy. We argue that strategic nutritional intervention through reversal of her metabolic syndrome using a medically-supervised ketogenic diet is a safe and effective treatment strategy in metabolic syndrome-associated pulmonary hypertension.

For as long as nucleic acids have been utilized to vertically and horizontally transfer genetic material, living organisms have had to develop methods of recognizing cytosolic DNA as either pathogenic (microbial invasion) or physiologic (mitosis and cellular proliferation). Derangement in key signaling molecules involved in these pathways of DNA sensing result in a family of diseases labeled interferonopathies. An interferonopathy, characterized by constitutive expression of type I interferons, ultimately manifests as severe autoimmune disease at a young age. Afflicted patients present with a constellation of immune-mediated conditions, including primary lung manifestations such as pulmonary fibrosis and pulmonary hypertension. The latter condition is especially interesting in light of the known role that DNA damage plays in a variety of types of inherited and induced pulmonary hypertension, with free DNA detection elevated in the circulation of affected individuals. While little is known regarding the role of cytosolic DNA sensing in development of pulmonary vascular disease, exciting new research in the related fields of immunology and oncology potentially sheds light on future areas of fruitful exploration. As such, the goal of this review is to summarize the state of the field of nucleic acid sensing, extrapolating common shared pathways that parallel our knowledge of pulmonary hypertension, in a molecular and cell-specific manner. Principles of DNA sensing related to known pulmonary injury inducing stimuli are also evaluated, in addition to potential therapeutic targets. Finally, future directions in pulmonary hypertension research and treatments will be briefly discussed.

Kai-Michael Beeh,1 Piotr Kuna,2 Massimo Corradi,3 Isabelle Viaud,4 Alessandro Guasconi,4 George Georges4 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Łódź, Poland; 3Department of Medicine and Surgery, University of Parma, Parma, Italy; 4Global Clinical Development, Chiesi Farmaceutici SpA, Parma, ItalyCorrespondence: Kai-Michael BeehInsaf Respiratory Research Institute, Wiesbaden, GermanyTel +49 611 9854347Email k.beeh@insaf-wi.deBackground: Three 52-week studies in COPD have assessed the efficacy and safety of single-inhaler extrafine formulation triple therapy combining beclomethasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) delivered via pressurized metered-dose inhaler (pMDI). BDP/FF/G is now being developed for delivery via multi-dose dry-powder inhaler (DPI; NEXThaler). This study aimed to demonstrate non-inferiority of BDP/FF/G DPI vs pMDI for lung function.Methods: Multicenter, randomized, double-blind, double-dummy, active-controlled, three-way cross-over study in patients with COPD and post-bronchodilator forced expiratory volume in 1 second (FEV1) 30– 80% predicted. Patients received BDP/FF/G 100/6/10μg via DPI and pMDI, and BDP/FF 100/6μg via pMDI, all two inhalations twice daily for four weeks, with treatments separated by two-week washout. The two co-primary objectives were to demonstrate non-inferiority between the two BDP/FF/G formulations for FEV1 area under the curve between 0 and 12 hours post-dose (AUC0-12h) normalized by time and trough FEV1 at 24 hours, both on Day 28. EudraCT 2017– 004405-41.Results: Of 449 patients screened, 366 were randomized, with 342 (93.4%) completing all three treatment periods. The primary objectives were met, with changes from baseline in FEV1 AUC0– 12h and trough FEV1 on Day 28 similar for the two BDP/FF/G formulations, and the confidence intervals for the difference lying entirely within the pre-specified non-inferiority criterion (– 50mL): – 20 (– 35, – 6) mL and 3 (– 15, 20) mL for AUC0– 12h and trough FEV1, respectively. BDP/FF/G pMDI and DPI were statistically superior to BDP/FF for these endpoints (p< 0.001). A similar proportion of patients experienced adverse events with each treatment (15.5%, 18.7% and 15.4% with BDP/FF/G DPI and pMDI, and BDP/FF, respectively); the majority were mild or moderate, with few related to treatment.Conclusion: Extrafine BDP/FF/G DPI and pMDI demonstrated similar efficacy and safety in patients with COPD, supporting the DPI formulation as a valid alternative.Keywords: adrenergic beta-2 receptor agonists, muscarinic antagonists, steroids, respiratory function tests, chronic obstructive pulmonary disease

Background: The aim of this study was to investigate inhaler device handling in elderly patients. Inhaler devices with respect to misuse and error correction were also compared. Methods: Inhaler use technique was assessed using standardized checklists at the first visit and 3-month follow-up visit after retraining. The primary outcome was difference in the acceptable use ratio among inhaler devices. Secondary outcomes included differences in error correction, the most common step of misuse, and factors affecting the accuracy of inhaler use. Results: A total of 251 patients (mean age, 76.4 years) were included. The handling of 320 devices was assessed in the study. All patients had been trained before. However, only 24.7% of them used inhalers correctly. Proportions of acceptable use for Evohaler, Respimat, Turbuhaler, Ellipta, and Breezhaler/Handihaler were 38.7%, 50.0%, 61.4%, 60.8%, and 43.2%, respectively (p=0.026). At the second visit, the acceptable use ratio had increased. There were no significant differences among inhaler types (Evohaler, 63.9%; Respimat, 86.1%; Turbuhaler, 74.3%; Ellipta, 64.6%; and Breezhaler/ Handihaler, 65.3% [p=0.129]). In multivariate analysis, body mass index, Turbuhaler, and Ellipta showed positive correlations with acceptable use of inhalers, whereas Chronic Obstructive Pulmonary Disease Assessment Test score showed a negative correlation. Conclusion: Although new inhalers have been developed, the accuracy of inhaler use remains low. Elderly patients showed more errors when using pressurized metered-dose inhalers than using dry powder inhalers and soft-mist inhalers. However, there were no significant differences in misuse among inhaler devices after individual training. Results of this study suggests that repeat training is more important than inhaler type.

Several clinical trials are being conducted worldwide to investigate the protective effect of the bacillus Calmette-Guerin (BCG) vaccine against death in healthcare providers who are working directly with coronavirus disease 2019 (COVID-19) patients. Clinical studies suggested that certain live vaccines, particularly the BCG vaccine, could reduce the mortality due to other diseases caused by non-targeted pathogens, most probably through the nonspecific effects (heterologous effects). By the end of May 2020, the available information on the COVID-19 pandemic indicated the great effect of the BCG vaccine in reducing the number of COVID-19 death cases. The occurrence of death due to COVID-19 was found to be 21-fold lower in countries with a national BCG vaccination policy than in countries without such a policy, based on the medians of COVID-19 death case per 1 million of the population in these two groups of countries (p

Rheumatoid arthritis (RA) is a systemic disease frequently involving the respiratory system. Organizing pneumonia (OP) is a defined pulmonary manifestation seen in patients with RA-associated interstitial lung disease. Even though OP following articular involvement is common, rarely it could be the first manifestation of RA. We herein report a case of 45-year-old female, who presented with OP as the first manifestation of RA with negative serology at presentation.

COVID-19 pneumonia is a serious health issue in the current pandemic caused by SARS-CoV-2. PCR testing is limited due to a number of factors and imaging has role in decision-making for many of these patients. We present computed tomography chest images of patients hospitalized with suspicion of COVID-19 pneumonia and point out the common and uncommon features on imaging to assist management of these patients.

Background The impact of underlying chronic respiratory diseases (CRDs) on the risk and mortality of patients with coronavirus disease 2019 (COVID-19) remains controversial. We aimed to investigate the effects of CRDs on the risk of COVID-19 and mortality among the population in South Korea. Methods The NHIS-COVID-19 database in South Korea was used for data extraction for this population-based cohort study. Chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), lung cancer, lung disease due to external agents, obstructive sleep apnea (OSA), and tuberculosis of the lungs (TB) were considered CRDs. The primary endpoint was a diagnosis of COVID-19 between January 1st and June 4th, 2020; the secondary endpoint was hospital mortality of patients with COVID-19. Multivariable logistic regression modeling was used for statistical analysis. Results The final analysis included 122,040 individuals, 7669 (6.3%) were confirmed as COVID-19 until 4 June 2020, and 251 patients with COVID-19 (3.2%) passed away during hospitalization. Among total 122,040 individuals, 36,365 individuals were diagnosed with CRD between 2015 and 2019: COPD (4488, 3.6%), asthma (33,858, 27.2%), ILD (421, 0.3%), lung cancer (769, 0.6%), lung disease due to external agents (437, 0.4%), OSA (550, 0.4%), and TB (608, 0.5%). Among the CRDs, patients either with ILD or OSA had 1.63-fold (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.17–2.26; P = 0.004) and 1.65-fold higher (OR 1.65, 95% CI 1.23–2.16; P P = 0.024) and 3.54-fold (OR 3.54, 95% CI 1.70–7.38; P Conclusions Patients with OSA and ILD might have an increased risk of COVID-19. In addition, COPD and chronic lung disease due to external agents might be associated with a higher risk of mortality among patients with COVID-19. Our results suggest that prevention and management strategies should be carefully performed.