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Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease.

STUDY OBJECTIVES: To determine whether an intensive weight-loss program (IWLP) is effective for reducing weight, the severity of obstructive sleep apnea (OSA), and metabolic variables in patients with obesity and severe OSA undergoing continuous positive airway pressure treatment. METHODS: Forty-two patients were randomized to the control (CG, n = 20) or the intervention group (IG, n = 22), who followed a 12-month IWLP. The primary outcome was a reduction in the apnea-hypopnea index (AHI) as measured at 3 and 12 months by full polysomnography. Metabolic variables, blood pressure, body fat composition by bioimpedance, carotid intima media thickness, and visceral fat by computed tomography were also assessed. RESULTS: Mean age was 49 (6.7) years, body mass index 35 (2.7) kg/m(2), and AHI 69 (20) events/h. Weight reduction was higher for the IG than the CG at 3 and 12 months, −10.5 versus −2.3 kg (P < .001), and −8.2 versus −0.1 kg (P < .001), respectively, as was loss of visceral fat at 12 months. AHI decreased more in the IG at 3 months (−23.72 versus −9 events/h) but the difference was not significant at 12 months, though 28% of patients from the IG had an AHI < 30 events/h compared to none in the CG (P = .046). At 12 months, the IG showed a reduction in C-reactive protein (P = .013), glycated hemoglobin (P = .031) and an increase in high density lipoprotein cholesterol (P = .027). CONCLUSIONS: An IWLP in patients with obesity and severe OSA is effective for reducing weight and OSA severity. It also results in an improvement in lipid profiles, glycemic control, and inflammatory markers. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Effectiveness of an Intensive Weight Loss Program for Obstructive Sleep Apnea Syndrome (OSAS) Treatment; Identifier: NCT02832414; URL: https://clinicaltrials.gov/ct2/show/record/NCT02832414 CITATION: López-Padrós C, Salord N, Alves C, et al. Effectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial. J Clin Sleep Med. 2020;16(4):503–514.

Purinergic and nitric oxide (NO) signaling pathways appear to be involved in the development of emphysema and vascular remodeling of chronic obstructive pulmonary disease (COPD). In an animal model, we evaluate the gene and protein expression of ENTPD1/CD39 and NT5E/CD73, and the effect on this expression of a guanylate cyclase (GC) stimulator. Forty-two guinea pigs underwent sham exposure (SHAM) or cigarette smoke (CS) exposure from three to six months. They were divided into six groups (sham-exposed, smokers or former smokers) and treated with vehicle (VH) or BAY 41-2272 (GC stimulator) for three months. Immunohistochemistry, western blot and qPCR assays were performed on lung tissue samples. Compared to SHAM + VH, ENTPD1 and NT5E were downregulated in the CS + VH group (1 ± 0 vs. 0.78 ± 0.51, p > 0.05, and 1 ± 0 vs. 0.45 ± 0.27, p = 0.027 respectively). Treatment with BAY 41-2722 increased ENTPD1 and NT5E expression to 1.06 ± 0.4 and 0.71 ± 0.35, respectively. No changes in the Ex-CS + BAY group were found. NT5E/CD73 was downregulated in the lungs of an animal model of emphysema. Treatment with a soluble GC stimulator tended to restore the gene and protein expression of ENTPD1/CD39 and NT5E/CD73 in smoke-exposed animals, suggesting its implication in a new mechanism for preventing emphysema.

BackgroundPatients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. Lung histological samples were scarce due to the high risk of contamination during autopsies. We aimed to correlate histological COVID-19 features with radiological findings through lung ultrasound (LU)-guided postmortem core needle biopsies (CNBs) and computerized tomography (CT) scans.MethodologyWe performed an observational prospective study, including 30 consecutive patients with severe COVID-19. The thorax was divided into 12 explorations regions to correlate LU and CT-scan features. Histological findings were also related to radiological features through CNBs.ResultsMean age was 62.56 ± 13.27 years old, with 96.7% male patients. Postmortem LU-guided CNBs were performed in 13 patients. Thirty patients were evaluated with both thoracic LU and chest CT scan, representing a total of 279 thoracic regions explored. The most frequent LU finding was B2-lines (49.1%). The most CT-scan finding was ground-glass opacity (GGO, 29%). Pathological CT-scan findings were commonly observed when B2-lines or C-lines were identified through LU (positive predictive value, PPV, 87.1%). Twenty-five postmortem echo-guided histological samples were obtained from 12 patients. Histological samples showed diffuse alveolar damage (DAD) (75%) and chronic interstitial inflammation (25%). The observed DAD was heterogeneous, showing multiple evolving patterns of damage, including exudative (33.3%), fibrotic (33.3%), and organizing (8.3%) phases. In those patients with acute or exudative pattern, two lesions were distinguished: classic hyaline membrane; fibrin “plug” in alveolar space (acute fibrinous organizing pneumonia, AFOP). C-profile was described in 33.3% and presented histological signs of DAD and lung fibrosis. The predominant findings were collagen deposition (50%) and AFOP (50%). B2-lines were identified in 66.7%; the presence of hyaline membrane was the predominant finding (37.5%), then organizing pneumonia (12.5%) and fibrosis (37.5%). No A-lines or B1-lines were observed in these patients.ConclusionLU B2-lines and C-profile are predominantly identified in patients with severe COVID-19 with respiratory worsening, which correspond to different CT patterns and histological findings of DAD and lung fibrosis.

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjogren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. We aimed to study the potential role of lung ultrasound score (LUS) in subjects with COVID-19. METHODS: We conducted an observational, prospective pilot study, including consecutive subjects admitted to an intermediate care unit due to COVID-19 pneumonia. LUS is a 12-zone examination method for lung parenchyma assessment. LUS was performed with a portable convex transducer, scores from 0 to 36 points. Clinical and demographic data were collected at LUS evaluation. Survival analysis was performed using a composite outcome including ICU admission or death. Subjects were followed for 30 d from LUS assessment. RESULTS: Of 36 subjects included, 69.4% were male, and mean age was 60.19 ± 12.75 y. A cutoff LUS ≥ 24 points showed 100% sensitivity, 69.2% specificity, and an area under the receiver operating characteristic curve of 0.85 for predicting worse prognosis. The composite outcome was present in 10 subjects (55.6%) with LUS ≥ 24 points, but not in the group with lower LUS scores (P < .001). Subjects with LUS ≥ 24 points had a higher risk of ICU admission or death (hazard ratio 9.97 [95% CI 2.75–36.14], P < .001). Significant correlations were observed between LUS and [Formula: see text] , serum D-dimer, C-reactive protein, lactate dehydrogenase, and lymphocyte count. CONCLUSIONS: LUS ≥ 24 points can help identify patients with COVID-19 who are likely to require ICU admission or to die during follow-up. LUS also correlates significantly with clinical and laboratory markers of COVID-19 severity.

In conclusion, we found for the first time a positive relationship between a long sleep duration and some markers of melanoma aggressiveness. Future studies are needed to investigate the main pathophysiological mechanisms that could explain this association and the prognostic relevance of this finding

Background and objective The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. Methods This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. Results In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. Conclusion In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

Background Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce. Methods A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs. Results Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11–3.13). Conclusions ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.

Idiopathic pulmonary fibrotic (IPF) patients present progressive worsening in quality of life (QoL) despite of anti-fibrotic medication. QoL includes different domains that require specific therapeutic approach. With the use of specific QoL questionnaires the impact of any integral patient support program (iPSP) may be measured. Methods: A home iPSP, which includes a trained nurse and physiotherapist that perform disease and treatment education, monitoring, and physiotherapy, is being conducted for 12 months, including the first month 4 visits, and then, 1 visit per month. Recruitment period was 6 months and all patients included from 22 sites received nintedanib (initiated at least one month later and not for more than 2 years). QoL (K-BILD) is measured at time 0,6 and 12 months. Results: In line with sample size calculation, a total of 90 patients have been recruited. Currently, 85 have completed the 6th-month follow-up visit. 83 could be analyzed (mean age 69.8, 75% males, 71% ex-smokers). 74% presented some comorbidity, cardiovascular disease was the most prevalent. Initial (V0) K-BILD mean value was 78. A significant improvement of QoL was observed at visit 6 (p=0.029). The best result was observed in the activity and dyspnea domain (p=0.002), followed by psychological (p=0.068) and symptoms domain (p=0.939). Improvement in these values was greater in those male patients older than 65 y. and in those who started the iPSP between 1 and 6 months after initiating nintedanib. Conclusion: iPSP conducted by trained nurses and physiotherapists, in treated IPF patients, improves their QoL especially in activity and psychological scores. The multidisciplinary managment is beneficial in these patients. Supported by Boehringer Ing

The incidence of gastrointestinal adverse events (AEs) associated with pirfenidone varies in IPF patients. We hypothesized that the type of dietary fatty acids (FA) affects digestibility and gastric motility, with a decrease in saturated-SFA or an increase in monounsaturated-MUFA. Objective: To compare the incidence of gastrointestinal AEs in patients with IPF initiating pirfenidone therapy, according to diet; MUFA vs SFA. Methods: 90 patients agreeing to maintain the same diet for 4 months were included. Allocation to SFA or MUFA-diet was determined by the Food Frequency Questionnaire (FFQ) assessed by an independent Central Committee. 7 centres, 4 in northern and 3 in southern Europe, have participated. Patient diet and AEs were recorded over 16 weeks; FVC and DLCO were measured at V1 and V5. Results: Interim results are based on 64 patients (38 MUFA and 26 SFA arm). Most patients were male (70%), mean age 71 (8.08), mean BMI 29 (without differences between groups). Baseline lung functions: FVC 81.5%, DLCO 55.4% for the MUFA group and FVC 75%, DLCO 44% for the SFA group. Except for the Netherlands, SFA diet was prevalent in the northern centres. Gastrointestinal AEs were reported in 31% of the SFA group and 17% of the MUFA group. Full dose of pirfenidone was taken by 73.1% of SFA and 94.7% of MUFA patients. Skin rash-photosensitivity did not differ between groups (1.2% and 1.5%, respectively). Medication withdraw was reported in 2 cases of SFA group. Conclusions: SFAdiet is associated with more gastrointestinal AEs during pirfenidone treatment in patients with IPF compared to MUFAdiet. Diet may be explored for improving medication adherence. Supported by Roche

Introduction: LAM is a rare and lethal disease characterized by progressive cystic lung destruction. Inhibition of mTOR with rapamycin is the current standard of care, which can slow-down disease. Plasma major histamine metabolite (Methylimidazoleacetic acid [MIAA]) is increased in LAM. Loratadine is a histamine receptor antagonist (HR1), which inhibits LAM cell proliferation. Therefore, a novel phase-II clinical trial for assessing safety and potential benefits of loratadine in LAM has been initiated. Methods:LORALAM clinical trial, phase-II, double-blind, randomized, placebo controlled, parallel-group, multicentre study initiates recruitment in July 2020. Enrollment plan includes 62 subjects with LAM on treatment with rapamycin ≥3 months, randomized 1:1 to add oral loratadine 10mg/day or placebo, once daily, for 52 weeks. Recruitment will end in June 2021. The primary endpoints are 1) to assess the safety profile of loratadine associated with rapamycin, 2) lung function decline after 52 weeks of treatment. The secondary endpoints are a) quality of life and progression free-survival time, b) changes in the established LAM serum biomarker VEGFD, c) the utility of MIAA for monitoring disease progression and biological treatment effect. Ethics and Dissemination: The study will be carried out in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and each ethical committee. This clinical trial contemplates the possibility of increasing the number of centers and including patients from patients support groups (LAM foundation, AELAM). Clinicaltrials.gov registered

Telomere dysfunction has been related to post-transplant morbi-mortality.Study aim´s: post-transplant survival and morbidity evaluation in fibrotic ILD with and without telomeropathy Methods: Prospective observational study of fibrotic ILD cases from Bellvitge Hospital that underwent lung transplant(LT) in V.Hebron Hospital. Telomere length was measured from lymphocytes DNA, through quantitative PCR. Whole-exome sequencing for telomere maintenance genes was performed in case of telomere shortening(TS) Results: 20 patients(IPF 40%, FPF 40%, hypersensitivity pneumonitis 5%, CPFE 5%, descamative interstitial pneumonia 5%, CTD-ILD 5%). Twelve(60%) patients had TS and mutations in RTEL1, TERT, DKC1,PARN. A similar pre-LT functional status was reported regardless of TS. LT morbidity: patients with TS had a greater need for extracorporeal circulation, longer ICU admission period and higher number of hospital admissions(p=0.033) with 2.9 times higher risk for readmission[(CI 1.11-7.59)(p=0.029)]; being the only ones with hematological complications during the first month. At long term, no differences in morbidity were found regardless of TS. Survival: 17/20(85%) patients,[10/12(83.3%) with TS and 7/8(87.5%) without]. Quality of life: overall mean FVC post-LT increase of 0.55 liters(p=0.0003)[CI95%: 0.21;0.89]. Oxygen withdrawal in 16/17(94.1%) cases with independence for daily life activities[15/17(88.2%)] and active life[11/17(64.7%)] regardless of TS(p=1.000) Conclusions: Post-LT morbidity differs accoding to elapsed time from LT and genetic susceptibility.However, a positive impact in post-LT survival and quality of life was shown for fibrotic ILD regardless of telomeropathy

Background: Bronchoscopy is a safe technique for diagnosing peripheral pulmonary lesions (PPLs), and virtual bronchoscopic navigation (VBN) helps guide the bronchoscope to PPLs. Objectives: We aimed to compare the diagnostic yield of VBN-guided and unguided ultrathin bronchoscopy (UTB) and explore clinical and technical factors associated with better results. We developed a diagnostic algorithm for deciding whether to use VBN to reach PPLs or choose an alternative diagnostic approach. Methods: We compared diagnostic yield between VBN-UTB (prospective cases) and unguided UTB (historical controls) and analyzed the VBN-UTB subgroup to identify clinical and technical variables that could predict the success of VBN-UTB. Results: Fifty-five cases and 110 controls were included. The overall diagnostic yield did not differ between the VBN-guided and unguided arms (47 and 40%, respectively; p = 0.354). Although the yield was slightly higher for PPLs ≤20 mm in the VBN-UTB arm, the difference was not significant (p = 0.069). No other clinical characteristics were associated with a higher yield in a subgroup analysis, but an 85% diagnostic yield was observed when segmentation was optimal and the PPL was endobronchial (vs. 30% when segmentation was suboptimal and 20% when segmentation was optimal but the PPL was extrabronchial). Conclusions: VBN-guided UTB is not superior to unguided UTB. A greater impact of VBN-guided over unguided UTB is highly dependent on both segmentation quality and an endobronchial location of the PPL. Segmentation quality should be considered before starting a procedure, when an alternative technique that may improve yield can be chosen, saving time and resources.

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR.

BACKGROUND AND OBJECTIVE The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications. METHODS Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis. RESULTS Family aggregation, age of

BACKGROUND The bronchial mucosa is protected by a specialized immune system focused on the prevention of colonization and infection by potentially pathogenic microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved in this mechanism. A defective immune barrier may facilitate the recurrent presence of PPMs in COPD. PURPOSE The aim of this study was to determine IgA-mediated bronchial specific immune responses against Pseudomonas aeruginosa in stable patients with severe disease. METHODS COPD patients with good-quality sputum samples obtained during stability were included and classified according to the presence or absence of chronic bronchial colonization by P. aeruginosa. Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and expressed as ratios, using the pooled level of 10 healthy subjects as reference (optical density450 patient/control). RESULTS Thirty-six stable COPD patients were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of specific IgA against P. aeruginosa in stable non-colonized patients were lower than those in healthy subjects (IgA ratio: median =0.15 [interquartile range {IQR} 0.05-0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59-2.79]) (p

Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases.In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed.Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (Funded by Insmed; WILLOW ClinicalTrials.gov number, NCT03218917.).

Background Airway stenting to restore airway patency in cases of malignant central airway obstruction is an effective palliation treatment. Our goal was to compare the efficacy after deployment and complications of a fully covered self-expandable metal stent (SEMS) (Aerstent) and a silicone stent (Dumon). Methods This was a retrospective cohort of 2 similar groups of patients with malignant central airway obstruction treated with stents between August 2012 and July 2017. Complications were assessed bronchoscopically. A competing risk for death analysis was performed to adjust the probability of developing a complication. Results Seventy patients (29 with silicone stents and 41 with SEMS) were included. Stent insertion was successful in all cases. Mucus retention was the most frequent complication (75.9% with silicone stents and 84.8% with SEMS; P = .51), followed by granulation tissue (51.7% with silicone stents and 41.3% with SEMS; P = .52) and migration (6.9% with silicone stents and 13.0% with SEMS; P = .47). In the first month, the cumulative incidence of a complication was 36.7% for silicone stents and 41.3% for SEMS and increased to 90.0% and 97.8% after 6 months, respectively (hazard ratio = 1.66; P = .04). A competing risk for death analysis showed an adjusted hazard ratio of 1.41 (P = .49) indicating no differences in overall complications between stents. Conclusions Both stents were equally successful and safe. The incidence of complications increased over time to 90% at 6 months for both stents. The risk of overall complications was higher for SEMS; nevertheless, when mortality was measured in a competitive risk analysis, no differences were found between SEMS and silicone stents.

Introduction and Aim: Pirfenidone and nintedanib are anti-fibrotic approved treatments for idiopathic pulmonary fibrosis (IPF). Its efficacy and safety in other fibrotic interstitial lung diseases (ILD) is under study in clinical trials. The aim was to analyse the effect of these drugs in non-IPF progressive fibrotic patients that couldn’t be included in these trials. Methods: Multicenter retrospective study of 34 progressive PF non-IPF patients treated with anti-fibrotic drugs. Demographic, clinical data and treatment-related variables were evaluated. The reason to start off-label anti-fibrotic was disease progression with previous therapy and exclusion from clinical trials. Results: Patients with non-IPF progressive PF were: 38% unclassifiable PF (UPF), 20% familial pulmonary fibrosis (FPF), 18% CTD-ILD, 15% chronic hypersensitivity pneumonitis (CHP) and 9% pneumoconiosis. Mean age was 67±12 years, 74% were male and 47% ex-smokers. 21% of cases had usual interstitial pneumonia HRCT pattern. Mean FVC was 66%±23 and DLCO 45%±12. Co-medications were: low-dose prednisone (20), mycophenolate (5) and sirolimus (1). Twenty-four subjects (71%) received pirfenidone and ten (29%) nintedanib. After one year, a FVC decrease of 5-10% was observed in only 3 patients (1 CHP, 1 pneumoconiosis, 1 UPF), while others showed stability or improvement. Main reported adverse effects were: 20% hypertransaminasemia, 27% diarrhea and 15% weight loss, requiring 5 patients to stop therapy. Conclusion: After one year of anti-fibrotic therapy, most patients with non-IPF progressive PF showed functional stability. Clinical trials are mandatory to evaluate their potential efficacy, but these drugs are a safe option in progressive PF patients.

Introduction: Fine particles matters (PM2.5) are the main component of indoor air pollution. Air pollution has been associated to poor asthma control. This study aims to compare the concentration of PM2.5 at home of patients with poor control asthma (PCA) versus good control asthma (GCA). Other objectives were to identify the domestic tasks or activities associated with the increase of PM2.5 concentration. Methodology: Observational study which analyzes the concentration of PM2.5 (μg/m3) measured by monitors located in the dining room and bedroom of asthmatic patients. Poor control asthma was defined by Asthma Control Questionnaire (ACQ)-5 more than 1.5 points. PM2.5 values minor than 20μg/m3 was defined as good air quality, between 21-80μg/m3 as moderate-high air pollution and higher than 80μg/m3 as unacceptably high levels of contamination. Demographic and clinical data, inflammation parameters and environmental contamination risk factors were collected in all patients. Results: A preliminary analysis of the first 15 patients included was performed (6 PCA and 9 GCA). PM2.5 peak values were 155 (63-226)μg/m3 at the dining room and 111 (72.5-262.5)μg/m3 at the bedroom in the GCA group. While in the PCA group, peak values were 130 (67.75-254.0)μg/m3 and 89 (56.5-138)μg/m3, respectively. No significant differences in demographic or clinical data were detected between groups. The use of spray lacquer and the proximity of an industrial factory or vehicle inspection service were the risk factors associated with the increase of indoor PM2.5. Conclusions: In the preliminary analysis, indoor higher levels of PM2.5 concentration were observed at home of asthma patients, irrespectively of disease control level measured by symptoms.

Background: Transbronchial lung cryobiopsy (TBLC) has been established as a common and safe procedure in the diagnosis of diffuse interstitial lung diseases (ILD). The patient can be discharged after a few hours under observation, except if a complication is presented, mainly bleeding or pneumothorax (PTX). Chest X-ray (CXR) is the conventional examination performed to detect PTX, but sometimes the delay in carrying it out may lengthen the patient’s hospital stay. Chest ultrasound (US) is more sensitive in the detection of PTX. Objective: to assess if chest US could replace CXR to detect PTX. Methods: prospective study in patients with indication of TBLC for the study of ILD from April 2018 to February 2019. Chest US was performed 1 hour after the procedure in the recovery area and a CXR was performed 4 hours after the procedure in the Radiology department, except if the patient had symptoms or if the US showed PTX, performing CXR earlier. Results: 32 patients were included,57.3% males.94% of the biopsies were performed in lower lobes.24 patients did not present PTX on US and this was confirmed with CXR, except in one patient who presented late PTX on the CXR.4 patients presented PTX on US and it was also confirmed with CXR. US detected 1 PTX that was not visible in CXR. In 3 cases there were doubts in the US image due to a bad window, of which 1 had PTX and another 2 did not. About the patients who presented PTX (22%), only two (6.2%) required a chest tube. The rest were discharged after 24-72 hours of observation. Conclusions: Chest US can replace conventional CXR in a large number of patients, allowing early discharge, although the possibility of late PTX (3.1%) must be taken into account.

Introduction: Surgical biopsy is the gold standard technique for the pathological diagnosis of diffuse interstitial lung diseases (ILD). Pulmonary cryobiopsy (PC) emerges as an alternative due to its reduction of surgical complications, maintaining an accurate diagnostic yield. However, complications are reported. It is still unclear if these complications could be related to technical, radiological or clinical features. Material and Methods: Retrospective descriptive study of consecutive patients who have undergone a PC for ILD diagnosis between 2012 and 2017. Mild bleeding was considered if only suction was necessary; moderate bleeding if balloon occlusion and cold serum instillation were required; and severe bleeding if a blocker was maintained and patients remainded intubated, or embolization was required. Severe pneumothorax was considered when thoracic drain was inserted. Technical aspects as well as clinical variables were confronted to type and degree of complications. Results: 117 patients were included, 55% male, average age was 61 y-o and 15% were smokers. Average lung function was FVC 86%, FEV1 85%, FEV1/FVC 80%, DLCO 61%. The main radiological findings were ground glass (41%) followed by reticular pattern (28%). In 32% of the cases fibrosis was present. Complications were described in 11.95%: bleeding (moderate 9.4%, severe 0.85%), pneumothorax (mild 0.85%, severe 0.85%), death 0%. PC could not be performed in 7% due to high traction-resistance. Conclusions: Pulmonary cryobiopsy is a safe technique, with a total complication rate of 11.95%, being severe complications rare (1.7%). In the described series, no association between complications and technical, clinical nor radiological features were found.

Currently, pulmonary tuberculosis (TB) isolation recommendations are based on serial sputum smear microscopy. To assess infectiousness of smear-negative/GeneXpert-positive (Sm-/GXpert+) pulmonary TB, we evaluated 511 contacts of pulmonary TB patients attended at a teaching hospital in Spain (2010–2018). There were no statistically significant differences in rates of Mycobacterium tuberculosis infection (46.2% contacts of smear-positive and 34.6% contacts of Sm-/GXpert+ pulmonary TB patients, p = 0.112). Sm-/GXpert+ pulmonary TB poses a substantial risk of transmission of M. tuberculosis infection. Our results add evidence to support including Real-time Polymerase Chain Reaction (XpertⓇMTB/RIF) in the work-up diagnosis of suspected pulmonary TB cases to make decisions on air-borne isolation.

Hyperbaric oxygen therapy, the administration of 100% oxygen at pressures > 1 atm, is believed to promote wound healing by increasing angiogenesis and collagen synthesis. To our knowledge, this treatment modality has never been described in patients with tracheal radionecrosis. Here, we report the case of a 55-year-old man diagnosed with stage IIIB lung adenocarcinoma who was treated with chemotherapy and concomitant external intensity-modulated radiotherapy involving the left lung and mediastinum. Nine months later, he presented with neck pain, cough with mucopurulent sputum, and fever. A PET-CT scan revealed a fissure in the posterior wall of the left upper trachea. Flexible bronchoscopy showed a tracheal ulceration with a small left posterior wall fissure that extended into the mediastinum. To our knowledge, this is the first report in the literature that suggests that treatment with hyperbaric oxygen therapy, local debridement, and antibiotics is a feasible and successful management option for patients with complicated tracheal radionecrosis.

The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was compared with that of salmeterol/fluticasone propionate in patients with stable, moderate-to-severe chronic obstructive pulmonary disease (COPD).AFFIRM COPD (Aclidinium and Formoterol Findings in Respiratory Medicine COPD) was a 24-week, double-blind, double-dummy, active-controlled study. Patients were randomised (1:1) to aclidinium/formoterol 400/12 µg twice-daily via Genuair/Pressair or salmeterol/fluticasone 50/500 µg twice-daily via Accuhaler. The primary end-point was peak forced expiratory volume in 1 s (FEV1) at week 24. Other end-points included Transition Dyspnoea Index (TDI) focal score at week 24, TDI and St George's Respiratory Questionnaire (SGRQ) responders, COPD Assessment Test and SGRQ scores, assessment of COPD symptoms and exacerbations, use of reliever medication, and device preference. Adverse events were monitored throughout.In total, 933 patients were eligible (mean age 63.4 years, 65.1% male). Aclidinium/formoterol was superior to salmeterol/fluticasone in peak FEV1 and noninferior in TDI. Health status and reduction in exacerbation risk were similar in both groups. While both treatments were well tolerated, pneumonia occurred less frequently with aclidinium/formoterol than salmeterol/fluticasone.In stable COPD, aclidinium/formoterol significantly improved bronchodilation versus salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk. Both treatments were well tolerated and treatment-related adverse events were less common with aclidinium/formoterol.

Resumen Introduccion Durante la pandemia de la gripe A (H1N1)pdm09 la obesidad emergio como un predictor signficativo de gravedad. El objetivo de este estudio fue investigar la asociacion entre el indice de masa corporal (IMC) y el riesgo de hospitalizacion por gripe. Metodos Pacientes hospitalizados (n = 755) con gripe confirmada por el laboratorio se emparejaron individualmente con pacientes ambulatorios (n = 783) con gripe confirmada por el laboratorio y con controles ambulatorios (n = 950) segun edad, fecha de ingreso/visita y provincia. El IMC se comparo mediante una regresion logistica condicional ajustada a los posibles factores de confusion (ORa). Se calculo la fraccion atribuible poblacional (FAP). Resultados Los valores elevados de IMC se asociaron a mayor riesgo de hospitalizacion, en comparacion con los casos ambulatorios (ORa = 1,11; IC 95%: 1,07-1,16) y con los controles ambulatorios (ORa = 1,04; IC 95%: 1,01-1,07). En comparacion con el peso normal, la obesidad tipo I , la obesidad tipo II y la obesidad tipo III se asociaron a mayor probabilidad de hospitalizacion, en comparacion con los casos ambulatorios (ORa = 1,85; IC 95%: 1,05-3,26; ORa = 5,24; IC 95%: 1,94-14,15 y ORa = 44,38; IC 95%: 4,47-440,5). En comparacion con el peso normal, la obesidad tipo II y la obesidad tipo III se asociaron a mayor probabilidad de hospitalizacion, en comparacion con los controles ambulatorios (ORa = 4,37; IC 95%: 1,79-10,69 y ORa = 4,95; IC 95%: 1,45-16,87). En los sujetos no vacunados de la gripe todas las categorias de IMC ≥ 30 kg/m 2 se asociaron a mayor probabilidad de hospitalizacion, en comparacion con el peso normal, tanto en los casos ambulatorios como en los controles ambulatorios. La FAP de hospitalizacion por gripe atribuible al IMC se situo entre el 21,9 y el 8,5%, y en los sujetos no vacunados de la gripe, entre el 20,5 y el 16,9%. Conclusion Un IMC elevado se asocia a mayor riesgo de hospitalizacion por gripe. Un alto porcentaje de los ingresos hospitalarios son atribuibles al IMC, especialmente en los sujetos no vacunados.

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.