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  • Prevalence and incidence of bronchiectasis in Italy
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-16
    Stefano Aliberti; Giovanni Sotgiu; Francesco Lapi; Andrea Gramegna; Claudio Cricelli; Francesco Blasi

    The understanding of the epidemiology of bronchiectasis is still affected by major limitations with very few data published worldwide. The aim of this study was to estimate the epidemiological burden of bronchiectasis in Italy in the adult population followed-up by primary care physicians. This study analyzed data coming from a large primary care database with 1,054,376 subjects in the period of time 2002–2015. Patients with bronchiectasis were selected by the use of International Statistical Classification of Diseases, 9th revision, Clinical Modification codes (ICD-9-CM). Patients with bronchiectasis were more likely to have a history of tuberculosis (0.47% vs. 0.06%, p < 0.0001), had higher rates of asthma (16.6% vs. 6.2%, p < 0.0001), COPD (23.3% vs. 6.4%, p < 0.0001) and rheumatoid arthritis (1.9% vs. 0.8%, p < 0.0001). The prevalence and incidence of bronchiectasis in primary care in Italy in 2015 were 163 per 100,000 population and 16.3 per 100,000 person-years, respectively. Prevalence and incidence increased with age and overall rates were highest in men over 75 years old. Prevalence and incidence computed after the exclusion of patients with a diagnosis of either asthma or COPD is 130 per 100,000 and 11.1 cases per 100,000 person-years, respectively. Bronchiectasis is not a rare condition in Italian adult population. Further studies are needed to confirm our results and provide a better insight on etiology of bronchiectasis in Italy. not applicable.

    更新日期:2020-01-17
  • Current infection control practices used in Australian and New Zealand cystic fibrosis centers
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-17
    Rebecca Elizabeth Stockwell; Michelle ELizabeth Wood; Emma Ballard; Vanessa Moore; Claire Elizabeth Wainwright; Scott Cameron Bell

    The 2013 update of the Infection Prevention and Control (IP&C) Guideline outlined recommendations to prevent the spread of CF respiratory pathogens. We aimed to investigate the current infection control practices used in Australian and New Zealand (NZ) CF centers. Two online surveys were distributed to Australian and NZ CF centers regarding the uptake of selected IP&C recommendations. One survey was distributed to all the Medical Directors and Lead CF Nurses and the second survey was distributed to all the Lead CF Physiotherapists. The response rate was 60% (60/100) for medical/nursing and 58% (14/24) for physiotherapy. Over 90% (55/60) of CF centers followed CF-specific infection control guidelines and consistent infection control practices were seen in most CF centers; 76% (41/54) had implemented segregation strategies for ambulatory care and no CF centers housed people with CF in shared inpatient accommodation. However, the application of contact precautions (wearing gloves and apron/gown) by healthcare professionals when reviewing a CF person was variable between CF center respondents but was most often used when seeing CF persons with MRSA infection in both ambulatory care and hospital admission (20/50, 40% and 42/45, 93% of CF centers, respectively). Mask wearing by people with CF was implemented into 61% (36/59) of centers. Hospital rooms were cleaned daily in 79% (37/47) of CF centers and the ambulatory care consult rooms were always cleaned between consults (49/49, 100%) and at the end of the clinic session (51/51, 100%); however the staff member tasked with cleaning changed with 37% (18/49) of CF centers responding that CF multidisciplinary team (MDT) members cleaned between patients whereas at the end of the clinic session, only 12% (6/51) of the CF MDT cleaned the consult room. Overall, Australian and NZ CF centers have adopted many recommendations from the IP&C. Although, the application of contact precautions was inconsistent and had overall a low level of adoption in CF centers. In ~ 25% of centers, mixed waiting areas occurred in the ambulatory care. Given the variability of responses, additional work is required to achieve greater consistency between centers.

    更新日期:2020-01-17
  • Size matters! Peripheral blood leukocyte telomere length and survival after critical illness
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Florian B. Mayr; Sachin Yende

    In 2009, Elizabeth Blackburn, Jack Szostak and Carol Greider were awarded the Nobel Prize in Physiology or Medicine for their pioneering work that led to the discovery of telomeres and the enzyme complex telomerase responsible for maintaining its structure [1]. Over the past four decades, the classic view of telomeres protecting the natural ends of linear chromosomes and telomerase as telomere-terminal transferase necessary for the replication of chromosome ends has significantly evolved. Many diverse fields have matured, including the discovery of key molecular components of telomerase, implications for limits to cellular replication, and identification and characterisation of human genetic disorders that result in premature telomere shortening [2]. The association of shorter leukocyte telomere length and reduced survival in critical illness may prove crucial in our quest to improve outcomes

    更新日期:2020-01-16
  • Patient reported outcomes for non-tuberculous mycobacterial disease
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Michael R. Loebinger; Surinder S. Birring

    The morbidity and mortality from non-tuberculous mycobacterial (NTM) disease is increasing [1]. Treatment of NTM usually requires multidrug regimens and is often associated with poor tolerability, significant side-effects and high failure rates. Not all patients with pulmonary NTM disease need treatment, and deciding who and when to treat can be challenging. The management of NTM is significantly hampered by the lack of reliable and responsive biomarkers to assess disease activity, progression and response to therapy, and at present, clinical decisions are made with a combination of symptom, radiology and microbiological assessments. There is a pressing need for new therapies and approaches for pulmonary NTM disease, and this will require robust clinical endpoints to evaluate them. There is a pressing need for patient related outcome measures for pulmonary NTM disease, to assist with both clinical management decisions and as an endpoint for clinical studies. This NTM Module should be considered an important step in this development.

    更新日期:2020-01-16
  • A regimen containing bedaquiline and delamanid compared to bedaquiline in patients with drug-resistant tuberculosis
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Olatunde Olayanju; Aliasgar Esmail; Jason Limberis; Keertan Dheda

    There are limited data on combining delamanid and bedaquiline in drug-resistant tuberculosis (DR-TB) regimens. Prospective long-term outcome data, including in HIV-infected persons, are unavailable. We prospectively followed up 122 South African patients (52.5% HIV-infected) with DR-TB and poor prognostic features between 2014 and 2018. We examined outcomes and safety in those who received a bedaquiline-based regimen (n=82) compared to those who received a bedaquiline–delamanid combination regimen (n=40). There was no significant difference in 6-month culture conversion (92.5% versus 81.8%; p=0.26) and 18-month favourable outcome rate (63.4% versus 67.5%; p=0.66) in the bedaquiline versus the bedaquiline–delamanid combination group, despite the latter having more advanced drug resistance (3.7% versus 22.5% resistant to at least five drugs; p=0.001) and higher pre-treatment failure rates (12.2% versus 52.5% with pre-treatment multidrug-resistant TB therapy failure; p<0.001). Although the proportion of prolongation of the QT interval corrected using Fridericia's formula was higher in the combination group (>60 ms from baseline (p=0.001) or >450 ms during treatment (p=0.001)), there were no symptomatic cases or drug withdrawals in either group. Results were similar in HIV-infected patients. A bedaquiline–delamanid combination regimen showed comparable long-term safety compared to a bedaquiline-based regimen in patients with DR-TB, irrespective of HIV status. These data inform regimen selection in patients with DR-TB from TB-endemic settings. A bedaquiline–delamanid combination regimen in drug-resistant tuberculosis patients with poor prognostic factors showed comparable efficacy and safety to those in a bedaquiline-based regimen

    更新日期:2020-01-16
  • A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Nikita Joshi; Satoshi Watanabe; Rohan Verma; Renea P. Jablonski; Ching-I Chen; Paul Cheresh; Nikolay S. Markov; Paul A. Reyfman; Alexandra C. McQuattie-Pimentel; Lango Sichizya; Ziyan Lu; Raul Piseaux-Aillon; David Kirchenbuechler; Annette S. Flozak; Cara J. Gottardi; Carla M. Cuda; Harris Perlman; Manu Jain; David W. Kamp; G.R. Scott Budinger; Alexander V. Misharin

    Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms. We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescence in situ hybridisation to a spatially restricted model of asbestos-induced pulmonary fibrosis. We demonstrate that tissue-resident alveolar macrophages, tissue-resident peribronchial and perivascular interstitial macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche. Deletion of monocyte-derived alveolar macrophages but not tissue-resident alveolar macrophages ameliorated asbestos-induced lung fibrosis. Monocyte-derived alveolar macrophages were specifically localised to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including platelet-derived growth factor subunit A. Using single-cell RNA sequencing and spatial transcriptomics in both humans and mice, we identified macrophage colony-stimulating factor receptor (M-CSFR) signalling as one of the novel druggable targets controlling self-maintenance and persistence of these pathogenic monocyte-derived alveolar macrophages. Pharmacological blockade of M-CSFR signalling led to the disappearance of monocyte-derived alveolar macrophages and ameliorated fibrosis. Our findings suggest that inhibition of M-CSFR signalling during fibrosis disrupts an essential fibrotic niche that includes monocyte-derived alveolar macrophages and fibroblasts during asbestos-induced fibrosis. Monocyte-derived alveolar macrophages orchestrate the development of the fibrotic niche, causally related to fibrosis and maintained via M-CSF/M-CSFR signalling

    更新日期:2020-01-16
  • Peripheral blood leukocyte telomere length is associated with survival of sepsis patients
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Shuo Liu; Chunxue Wang; Gary Green; Hanjing Zhuo; Kathleen D. Liu; Kirsten N. Kangelaris; Antonio Gomez; Alejandra Jauregui; Kathryn Vessel; Serena Ke; Carolyn Hendrickson; Michael A. Matthay; Carolyn S. Calfee; Lorraine B. Ware; Paul J. Wolters

    Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study. We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF). In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1–1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2–2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2–2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2–2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1–6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort. Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness. Shorter peripheral blood leukocyte telomere length is strongly associated with worse survival and more severe ARDS in critically ill patients with sepsis

    更新日期:2020-01-16
  • Preliminary validation of the NTM Module: a patient-reported outcome measure for patients with pulmonary nontuberculous mycobacterial disease
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Emily Henkle; Kevin L. Winthrop; Gregory P. Ranches; Wesley Plinke; Hana K. Litvin; Alexandra L. Quittner

    Introduction Nontuberculous mycobacteria (NTM) cause chronic, debilitating pulmonary disease. Patient-reported outcomes provide measures of symptoms, functioning and treatment response. Here we describe the preliminary validation of the recently developed NTM Module. Methods The study population included Northwest NTM Biobank patients in whom Mycobacterium avium complex (MAC) was isolated and who had ever met the 2007 American Thoracic Society/Infectious Diseases Society of America pulmonary disease criteria. The NTM Module was administered at enrolment and 12 months; a subset also completed the Quality of Life Questionnaire–Bronchiectasis (QOL-B). The NTM Module generates four domain scores (0–100; higher scores indicate better functioning) reflecting NTM-specific symptoms (NTM Symptoms, Body Image, Digestive Symptoms and Eating Problems). We described patient characteristics and mean scores, and evaluated psychometric properties, including response to treatment at 12 months, for each domain. Results Overall, 203 patients with pulmonary MAC disease were included. Average enrolment scores ranged from 76 (NTM Symptoms) to 84 (Eating Problems). Ceiling effects were observed for Body Image (26% of participants) and Eating Problems (52%). Internal consistency (Cronbach's alpha) ranged from 0.67 (Digestive Symptoms) to 0.89 (Eating Problems). The intraclass correlation for test–retest reproducibility (n=27) ranged from 0.72 (Body Image) to 0.94 (Eating Problems). Patients starting treatment (n=35) had statistically significant increases in scores for NTM Symptoms (+5, p=0.04), Digestive Symptoms (+7, p=0.002), Body Image (+7, p=0.03) and QOL-B Respiratory Symptoms (n=25, +10, p=0.006). NTM Symptoms scores increased by 15 points (p=0.002) in the 16 patients with scores ≤80 at enrolment. Conclusion The NTM Module generally performs well as a valid patient-reported outcome for pulmonary MAC disease and was responsive to MAC treatment. The NTM Symptom Module is a valid patient-reported outcome tool that can facilitate patient-centred care and may be used as an outcome in clinical trials to support labelling claims for regulatory bodies.

    更新日期:2020-01-16
  • Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Elisabeth Arndal; Helle K. Johansen; Janus A.J. Haagensen; Jennifer A. Bartell; Rasmus L. Marvig; Mikkel Alanin; Kasper Aanæs; Niels Høiby; Kim G. Nielsen; Vibeke Backer; Christian von Buchwald

    Similar to patients with cystic fibrosis (CF) and non-CF bronchiectasis, patients with primary ciliary dyskinesia (PCD) are prone to recurrent or chronic lung infections with Pseudomonas aeruginosa . Chronic P. aeruginosa lung infection has a prevalence of up to 39% in patients with PCD [1] and is associated with structural damage, affecting lung function. Treatment of P. aeruginosa infection is challenging because P. aeruginosa adapts to the host environment through genotypic/phenotypic changes, promoting a reduced immune response [2]. For the first time it is shown that the same Pseudomonas aeruginosa clone exists in both the upper and lower airways in patients with PCD, providing a solid support of the unified airway theory where the sinuses are a possible bacterial reservoir

    更新日期:2020-01-16
  • What kind of emphasis do we need in clinical research to enable personalised respiratory medicine?
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Igor Gonda

    The manifesto proposed by Roche et al . [1] is a most important plan to revolutionise respiratory clinical research. It also prompts a key question about the balance between the effort spent on randomised clinical trials (RCTs) versus real-life research (RLR), particularly in an era where frequent monitoring of patients capturing their real life, using wearable devices, home diagnostics, smartphones, smart inhalers, collections of contextual information, cloud connectivity and the ability to analyse large complex datasets is becoming increasingly feasible [2]. Real-life clinical research may be more valuable to achieve the aspirations of personalised medicine than the traditional “regulatory style” randomised clinical trials

    更新日期:2020-01-16
  • Connected real-life research, a pillar of P4 medicine
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Nicolas Roche; Antonio Anzueto; Sinthia Bosnic Anticevich; Alan Kaplan; Marc Miravitlles; Dermot Ryan; Joan B. Soriano; Omar Usmani; Nikos Papadopoulos; G. Walter Canonica

    We thank I. Gonda for outlining the promises and challenges of real-life research (RLR), following the publication of the Respiratory Effectiveness Group manifesto in the European Respiratory Journal [1]. As outlined in this correspondence, the ultimate goal of RLR is to improve patients' outcomes through more precise decision-making in the current era of personalised medicine. To this aim, RLR provides evidence complementing randomised controlled trials (RCTs), especially exploring benefit–risk–cost ratios in both large and specific subpopulations, while minimising the Hawthorne effect. I. Gonda underlines a particularly important aspect of RLR, i.e. how it can be revolutionised by new technologies. This is especially promising in the respiratory field, where therapy administered with inhalation devices plays a major role, while many chronic conditions are under the influence of environmental conditions that can now be continuously recorded. Assessment of m-Health tools needs to include high-quality real-life research studies. Reciprocally, real-life research can benefit highly from opportunities offered by connected devices.

    更新日期:2020-01-16
  • Nazartinib in EGFR Thr790Met-mutant non-small-cell lung cancer
    Lancet Respir. Med. (IF 22.992) Pub Date : 2020-01-15
    Jacek Jassem; Rafał Dziadziuszko
    更新日期:2020-01-16
  • Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study
    Lancet Respir. Med. (IF 22.992) Pub Date : 2020-01-15
    Daniel S-W Tan; Natasha B Leighl; Gregory J Riely; James C-H Yang; Lecia V Sequist; Juergen Wolf; Takashi Seto; Enriqueta Felip; Santiago P Aix; Maud Jonnaert; Chun Pan; Eugene Y Tan; Jinnie Ko; Susan E Moody; Dong-Wan Kim
    更新日期:2020-01-16
  • αAzithromycin has enhanced effects on lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients compared to controls
    Respir. Res. (IF 3.829) Pub Date : 2020-01-15
    Kristina Krempaska; Sandra Barnowski; Jacopo Gavini; Nina Hobi; Simone Ebener; Cedric Simillion; Andrea Stokes; Ronja Schliep; Lars Knudsen; Thomas K. Geiser; Manuela Funke-Chambour

    Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease without a cure and new drug strategies are urgently needed. Differences in behavior between diseased and healthy cells are well known and drug response can be different between cells isolated from IPF patients and controls. The macrolide Azithromycin (AZT) has anti-inflammatory and immunomodulatory properties. Recently anti-fibrotic effects have been described. However, the anti-fibrotic effects on primary IPF-fibroblasts (FB) directly compared to control-FB are unknown. We hypothesized that IPF-FB react differently to AZT in terms of anti-fibrotic effects. Primary normal human lung and IPF-FB were exposed to TGF-β (5 ng/ml), Azithromycin (50 μM) alone or in combination prior to gene expression analysis. Pro-collagen Iα1 secretion was assessed by ELISA and protein expression by western blot (αSMA, Fibronectin, ATP6V1B2, LC3 AB (II/I), p62, Bcl-xL). Microarray analysis was performed to screen involved genes and pathways after Azithromycin treatment in control-FB. Apoptosis and intraluminal lysosomal pH were analyzed by flow cytometry. AZT significantly reduced collagen secretion in TGF-β treated IPF-FB compared to TGF-β treatment alone, but not in control-FB. Pro-fibrotic gene expression was similarly reduced after AZT treatment in IPF and control-FB. P62 and LC3II/I western blot revealed impaired autophagic flux after AZT in both control and IPF-FB with significant increase of LC3II/I after AZT in control and IPF-FB, indicating enhanced autophagy inhibition. Early apoptosis was significantly higher in TGF-β treated IPF-FB compared to controls after AZT. Microarray analysis of control-FB treated with AZT revealed impaired lysosomal pathways. The ATPase and lysosomal pH regulator ATP6V0D2 was significantly less increased after additional AZT in IPF-FB compared to controls. Lysosomal function was impaired in both IPF and control FB, but pH was significantly more increased in TGF-β treated IPF-FB. We report different treatment responses after AZT with enhanced anti-fibrotic and pro-apoptotic effects in IPF compared to control-FB. Possibly impaired lysosomal function contributes towards these effects. In summary, different baseline cell phenotype and behavior of IPF and control cells contribute to enhanced anti-fibrotic and pro-apoptotic effects in IPF-FB after AZT treatment and strengthen its role as a new potential anti-fibrotic compound, that should further be evaluated in clinical studies.

    更新日期:2020-01-15
  • Evaluation of sleep quality and daytime somnolence in patients with chronic obstructive pulmonary disease in pulmonary rehabilitation
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-15
    Leandro Nobeschi; Juliana Zangirolami-Raimundo; Priscila Kessar Cordoni; Selma Denis Squassoni; Elie Fiss; Andrés Ricardo Pérez-Riera; Luiz Carlos de Abreu; Rodrigo Daminello Raimundo

    Dyspnea, fatigue, and decline in sleep quality are symptoms of chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation programs have been shown to ameliorate dyspnea and fatigue. However, only a few studies have investigated the effects of pulmonary rehabilitation on the sleep quality of COPD patients. In this study, we analyzed the benefits of a pulmonary rehabilitation program to sleep quality and daytime somnolence in COPD patients. This study was a study of 30 moderate-severe COPD patients. All patients were evaluated by a pulmonologist and underwent polysomnography before participating in the study. For this study, we selected only ex-smokers and patients with sleep apnea were referred to the sleep clinic. These participants were prospectively recruited and not selected based on program completion. Before the start of the program, sleep quality and daytime somnolence of the participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Rehabilitation program consisted of muscular training sessions conducted at the gym 3 times per week for 12 weeks. After rehabilitation program, the patients were reassessed and their sleep quality and daytime somnolence were reevaluated using the PSQI and the ESS, respectively. Before rehabilitation, PSQI evaluation revealed that 73% of the participants had poor sleep quality, and ESS evaluation showed that 86.7% of the participants experienced daytime somnolence. After pulmonary rehabilitation, the PSQI specifically improved in terms of subjective sleep quality and sleep duration (< 0.001), habitual sleep efficiency (0.001), and sleep latency and sleep alterations (0.002) and there was also improvement in the ESS (< 0.001). Pulmonary rehabilitation program of gradually increasing intensity has the potential to provide sleep-related benefits to patients with COPD who have poor sleep quality and daytime somnolence. Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR62b4z2.

    更新日期:2020-01-15
  • Fluid intake-related association between urine output and mortality in acute respiratory distress syndrome
    Respir. Res. (IF 3.829) Pub Date : 2020-01-14
    Yanfei Shen; Guolong Cai; Shangzhong Chen; Caibao Hu; Jing Yan

    Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98–0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69–0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03–0.253, P < 0.001); this association was not significant for patients with UO/FI ratios > 0.5 (OR: 1.04, 95% CI: 0.96–1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96–0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

    更新日期:2020-01-15
  • Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: a randomised clinical trial
    Thorax (IF 9.640) Pub Date : 2020-01-14
    Claire L Boswell-Ruys; Chaminda R H Lewis; Nirupama S Wijeysuriya; Rachel A McBain; Bonsan Bonne Lee; David K McKenzie; Simon C Gandevia; Jane E Butler

    Background Respiratory complications remain a leading cause of morbidity and mortality in people with acute and chronic tetraplegia. Respiratory muscle weakness following spinal cord injury-induced tetraplegia impairs lung function and the ability to cough. In particular, inspiratory muscle strength has been identified as the best predictor of the likelihood of developing pneumonia in individuals with tetraplegia. We hypothesised that 6 weeks of progressive respiratory muscle training (RMT) increases respiratory muscle strength with improvements in lung function, quality of life and respiratory health. Methods Sixty-two adults with tetraplegia participated in a double-blind randomised controlled trial. Active or sham RMT was performed twice daily for 6 weeks. Inspiratory muscle strength, measured as maximal inspiratory pressure (PImax) was the primary outcome. Secondary outcomes included lung function, quality of life and respiratory health. Between-group comparisons were obtained with linear models adjusting for baseline values of the outcomes. Results After 6 weeks, there was a greater improvement in PImax in the active group than in the sham group (mean difference 11.5 cmH2O (95% CI 5.6 to 17.4), p<0.001) and respiratory symptoms were reduced (St George Respiratory Questionnaire mean difference 10.3 points (0.01–20.65), p=0.046). Significant improvements were observed in quality of life (EuroQol-Five Dimensional Visual Analogue Scale 14.9 points (1.9–27.9), p=0.023) and perceived breathlessness (Borg score 0.64 (0.11–1.17), p=0.021). There were no significant improvements in other measures of respiratory function (p=0.126–0.979). Conclusions Progressive RMT increases inspiratory muscle strength in people with tetraplegia, by a magnitude which is likely to be clinically significant. Measurement of baseline PImax and provision of RMT to at-risk individuals may reduce respiratory complications after tetraplegia. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808).

    更新日期:2020-01-15
  • RAGE-induced ILC2 expansion in acute lung injury due to haemorrhagic shock
    Thorax (IF 9.640) Pub Date : 2020-01-14
    Kai Zhang; Yue Jin; Dengming Lai; Jieyan Wang; Yang Wang; Xiaoliang Wu; Melanie Scott; Yuehua Li; Jinchao Hou; Timothy Billiar; Mark Wilson; Qiang Shu; Xiangming Fang; Jie Fan

    Background Type 2 immune dysfunction contributes to acute lung injury and lethality following haemorrhagic shock (HS) and trauma. Group 2 innate lymphoid cells (ILC2s) play a significant role in the regulation of type 2 immune responses. However, the role of ILC2 in post-HS acute lung injury and the underlying mechanism has not yet been elucidated. Objective To investigate the regulatory role of ILC2s in HS-induced acute lung injury and the underlying mechanism in patients and animal model. Methods Circulating markers of type 2 immune responses in patients with HS and healthy controls were characterised. Using a murine model of HS, the role of high-mobility group box 1 (HMGB1)-receptor for advanced glycation end products (RAGE) signalling in regulation of ILC2 proliferation, survival and function was determined. And the role of ILC2 in inducing type 2 immune dysfunction was assessed as well. Results The number of ILC2s was significantly increased in the circulation of patients with HS that was correlated with the increase in the markers of type 2 immune responses in the patients. Animal studies showed that HMGB1 acted via RAGE to induce ILC2 accumulation in the lungs by promoting ILC2 proliferation and decreasing ILC2 death. The expansion of ILC2s resulted in type 2 cytokines secretion and eosinophil infiltration in the lungs, both of which contributed to lung injury after HS. Conclusions These results indicate that HMGB1-RAGE signalling plays a critical role in regulating ILC2 biological function that aggravates type 2 lung inflammation following HS.

    更新日期:2020-01-15
  • Integrated proteogenomic approach identifying a protein signature of COPD and a new splice variant of SORBS1
    Thorax (IF 9.640) Pub Date : 2020-01-14
    Corry-Anke Brandsma; Victor Guryev; Wim Timens; Ana Ciconelle; Dirkje S Postma; Rainer Bischoff; Maria Johansson; Ekaterina S Ovchinnikova; Johan Malm; Gyorgy Marko-Varga; Thomas E Fehniger; Maarten van den Berge; Peter Horvatovich

    Translation of genomic alterations to protein changes in chronic obstructive pulmonary disease (COPD) is largely unexplored. Using integrated proteomic and RNA sequencing analysis of COPD and control lung tissues, we identified a protein signature in COPD characterised by extracellular matrix changes and a potential regulatory role for SUMO2. Furthermore, we identified 61 differentially expressed novel, non-reference, peptides in COPD compared with control lungs. This included two peptides encoding for a new splice variant of SORBS1, of which the transcript usage was higher in COPD compared with control lungs. These explorative findings and integrative proteogenomic approach open new avenues to further unravel the pathology of COPD.

    更新日期:2020-01-15
  • Young non-smoker diagnosed with lung cancer
    Lancet Respir. Med. (IF 22.992) Pub Date : 2020-01-14
    Tony Kirby
    更新日期:2020-01-15
  • Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-14
    Sae Byol Kim; Beomsu Shin; Ji-Ho Lee; Seok Jeong Lee; Myoung Kyu Lee; Won-Yeon Lee; Suk Joong Yong; Sang-Ha Kim

    Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002–1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239–2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

    更新日期:2020-01-14
  • COPD and asthma in patients with opioid dependency: a cross-sectional study in primary care
    npj Prim. Care Respir. Med. (IF 2.820) Pub Date : 2020-01-14
    S. Mehta; N. Parmar; M. Kelleher; C. J. Jolley; P. White; S. Durbaba; M. Ashworth

    Patients treated for drug addiction have high asthma and COPD prevalence rates. The relative contributions of cigarette smoking, smoking intensity and possible smoking of other substances has not been described. We aimed to describe the prevalence and determinants of asthma and COPD in patients prescribed methadone as opioid substitution therapy (OST). In a cross-sectional study of an anonymised patient-level primary care dataset of UK inner-city general practices (n = 46), 321,395 patients aged ≥18 years were identified. A total of 676 (0.21%) had a record of a methadone ever issued in primary care. The association between respiratory disease and methadone prescribing was examined using logistic regression. Models were adjusted for potential effects of clustering by practice. A total of 97.3% of patients prescribed methadone were cigarette smokers, either current (81.2%) or ex-smokers (16.1%). The prevalences of asthma and COPD were higher in methadone patients (14.2% and 12.4%, respectively) compared to non-methadone patients (4.4% and 1.1%, respectively). Methadone was an independent determinant of asthma, adjusting for smoking status (OR 3.21; 95% CI: 2.52, 4.10) or for smoking intensity (3.08; 2.27, 4.19), and of COPD, adjusting for smoking status (6.00; 4.61, 7.80) or for smoking intensity (5.80; 4.12, 8.17). COPD and asthma prevalence were substantially higher in those prescribed methadone compared to those never prescribed methadone. Prescription of methadone was an independent predictor for both COPD and asthma, even after adjustment for smoking status and smoking intensity. Possible explanations include confounding by association with smoking of heroin or crack cocaine, both of which may have a causal association with COPD and asthma.

    更新日期:2020-01-14
  • A comparison of tiotropium, long-acting β2-agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Christian Vogelberg; Stanley Goldstein; LeRoy Graham; Alan Kaplan; Alberto de la Hoz; Eckard Hamelmann

    Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting β2-agonists (LABAs), leukotriene receptor antagonists (LTRAs) and long-acting muscarinic antagonists (LAMAs) as add-on treatment to ICS in children and adolescents aged 4–17 years. A literature search identified a total of 29 studies that met the inclusion criteria, including 21 randomised controlled trials (RCTs) of LABAs versus placebo, two RCTs of LAMAs (tiotropium) versus placebo, and four RCTs of LTRA (montelukast), all as add-on to ICS. In these studies, tiotropium and LABAs provided greater improvements in lung function than LTRAs, when compared with placebo as add-on to ICS. Although exacerbation data were difficult to interpret, tiotropium reduced the risk of exacerbations requiring oral corticosteroids when added to ICS, with or without additional controllers. LABAs and LTRAs had a comparable risk of asthma exacerbations with placebo when added to ICS. When adverse events (AEs) or serious AEs were analysed, LABAs, montelukast and tiotropium had a comparable safety profile with placebo. In conclusion, this literature review provides an up-to-date overview of the efficacy and safety of LABAs, LTRAs and LAMAs as add-on to ICS in children and adolescents with asthma. Overall, tiotropium and LABAs have similar efficacy, and provide greater improvements in lung function than montelukast as add-on to ICS. All three controller options have comparable safety profiles.

    更新日期:2020-01-14
  • Extracorporeal membrane oxygenation as a bridge to lung transplantation: analysis of Korean organ transplantation registry (KOTRY) data
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Ryoung-Eun Ko; Jin Gu Lee; Song Yee Kim; Young Tae Kim; Sun Mi Choi; Do Hyung Kim; Woo Hyun Cho; Seung-Il Park; Kyung-Wook Jo; Hong Kwan Kim; Hyo Chae Paik; Kyeongman Jeon

    The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation has greatly increased. However, data regarding the clinical outcomes of this approach are lacking. The objective of this multicenter prospective observational cohort study was to evaluate lung transplantation outcomes in Korean Organ Transplantation Registry (KOTRY) patients for whom ECMO was used as a bridge to transplantation. Between March 2015 and December 2017, a total of 112 patients received lung transplantation and were registered in the KOTRY, which is a prospective, multicenter cohort registry. The entire cohort was divided into two groups: the control group (n = 85, 75.9%) and bridge-ECMO group (n = 27, 24.1%). There were no significant differences in pre-transplant and intraoperative characteristics except for poorer oxygenation, more ventilator use, and longer operation time in the bridge-ECMO group. The prevalence of primary graft dysfunction at 0, 24, 48, and 72 h after transplantation did not differ between the two groups. Although postoperative hospital stays were longer in the bridge-ECMO group than in the control group, hospital mortality did not differ between the two groups (25.9% vs. 13.3%, P = 0.212). The majority of patients (70.4% of the bridge-ECMO group and 77.6% of the control group) were discharged directly to their homes. Finally, the use of ECMO as a bridge to lung transplantation did not significantly affect overall survival and graft function. Short- and long-term post-transplant outcomes of bridge-ECMO patients were comparable to recipients who did not receive ECMO.

    更新日期:2020-01-14
  • REALizing and improving management of stable COPD in China: a multi-center, prospective, observational study to realize the current situation of COPD patients in China (REAL) – rationale, study design, and protocol
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-13
    Ting Yang; Baiqiang Cai; Bin Cao; Jian Kang; Fuqiang Wen; Wanzhen Yao; Jinping Zheng; Xia Ling; Hongyan Shang; Chen Wang

    Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China. The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients’ usual care visits, and by telephone interview every 3 months. Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019. ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

    更新日期:2020-01-14
  • Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-13
    Lara Pisani; Sara Betti; Carlotta Biglia; Luca Fasano; Vito Catalanotti; Irene Prediletto; Vittoria Comellini; Letizia Bacchi-Reggiani; Stefano Nava FERS

    Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the “pure” COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). HFNC is able to significantly decrease the level of PaCO2 after 72 h only in “pure” COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.

    更新日期:2020-01-14
  • A critical approach to personalised medicine in ARDS
    Lancet Respir. Med. (IF 22.992) Pub Date : 2020-01-13
    Lorenzo Ball; Pedro L Silva; Patricia R M Rocco; Paolo Pelosi
    更新日期:2020-01-14
  • 更新日期:2020-01-14
  • Development and validation of parsimonious algorithms to classify acute respiratory distress syndrome phenotypes: a secondary analysis of randomised controlled trials
    Lancet Respir. Med. (IF 22.992) Pub Date : 2020-01-13
    Pratik Sinha; Kevin L Delucchi; Daniel F McAuley; Cecilia M O'Kane; Michael A Matthay; Carolyn S Calfee
    更新日期:2020-01-14
  • Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Amaia Artaraz; Megan L. Crichton; Simon Finch; Hani Abo-Leyah; Pieter Goeminne; Stefano Aliberti; Thomas Fardon; James D. Chalmers

    Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12 months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r = 0.61, p = 0.0037, Leicester Cough Questionnaire, r = − 0.52,p = 0.0015, St Georges Respiratory Questionnaire, r = 0.61,p < 0.0001 and 6 min walk test, r = − 0.46,p = 0.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3 days (SD 5.7). A minimum clinically important difference of 4 points is proposed. The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials.

    更新日期:2020-01-13
  • Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Lídia Perea; Ana Rodrigo-Troyano; Elisabet Cantó; Marisol Domínguez-Álvarez; Jordi Giner; Ferran Sanchez-Reus; Judit Villar-García; Sara Quero; Marian García-Núñez; Alicia Marín; Eduard Monsó; Rosa Faner; Alvar Agustí; Silvia Vidal; Oriol Sibila

    For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0–319.6) vs. 273.4 (203.1–426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35–15.3) vs. 15.6 (2.0–29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

    更新日期:2020-01-13
  • ZDHXB-101 (3′,5-Diallyl-2, 4′-dihydroxy-[1,1′-biphen-yl]-3,5′-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Jun-xia Jiang; Hui-juan Shen; Yan Guan; Yong-liang Jia; Jian Shen; Qi Liu; Qiang-min Xie; Xiao-feng Yan

    Airway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks. The expression of sEH and CYP2J2, the level of 14, 15-epoxyeicosatrienoic acids (EETs), airway remodeling, hyperresponsiveness and inflammation were analyzed to determine the inhibition of sEH. The intragastric administration of 3 or 10 mg/kg ZDHXB-101, which is a structural derivative of natural product honokiol and a novel soluble epoxide hydrolase (sEH) inhibitor, daily for 9 weeks significantly increased the level of 14, 15-EETs by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. ZDHXB-101 reduced the expression of remodeling-related markers such as interleukin (IL)-13, IL-17, MMP-9 N-cadherin, α-smooth muscle actin, S100A4, Twist, goblet cell metaplasia, and collagen deposition in the lung tissue or in bronchoalveolar lavage fluid. Moreover, ZDHXB-101 alleviated AHR, which is an indicator that is used to evaluate the airway remodeling function. The inhibitory effects of ZDHXB-101 were demonstrated to be related to its direct inhibition of the extracellular signal-regulated kinase (Erk1/2) phosphorylation, as well as inhibition of c-Jun N-terminal kinases (JNK) and the signal transducer and activator of transcription-3 (STAT3) signal transduction. These findings first revealed the anti-remodeling potential of ZDHXB-101 lead in chronic airway disease.

    更新日期:2020-01-13
  • Neuromuscular blocking agents for acute respiratory distress syndrome: an updated meta-analysis of randomized controlled trials
    Respir. Res. (IF 3.829) Pub Date : 2020-01-13
    Zhongjun Zheng; Libing Jiang; Song Zhang; Christophe Guervilly; Mao Zhang; Xia Feng; Jianbo Ding

    The aim of this study is investigating the benefits and harms of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS). We comprehensively searched PubMed, EMBASE, and Cochrane library for randomized controlled trials comparing NMBAs to any other comparator. We pooled data using relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals. We assessed the quality of included studies using the Cochrane tool and levels of evidence using the GRADE method. Finally, six RCTs (n = 1557 patients) were eligible for analysis. The results showed NMBAs use was not associated with reduced 28 days mortality (RR 0.78; 95% CI, 0.58 to 1.06; P = 0.11), 90 days mortality (RR, 0.92; 95% CI, 0.81 to 1.04; P = 0.16), and intensive care unit (ICU) mortality (RR, 0.90; 95% CI, 0.79 to 1.03; P = 0.13) in patients with ARDS. However, 21–28 days mortality was slightly lower in patients received NMBAs (RR 0.73; 95% CI, 0.54 to 0.99; P = 0.04; I2 = 53%). Besides, NMBAs use could improve the PaO2/FiO2 ratio at 48 and 72 h, decrease plateau pressure and PEEP at 72 h. Additionally, NMBAs had no significant effects on days free of ventilation at day 28 (WMD, 0.55; 95% CI, − 0.46 to 1.57; P = 0.29), days not in ICU at day 28 (WMD, 0.12; 95% CI, − 0.85 to 1.08; P = 0.82), ICU-acquired weakness (RR, 1.23; 95% CI, 0.99 to 1.93; P = 0.06). Finally, NMBAs use was associated with a lower risk of barotrauma (RR, 0.55; 95% CI, 0.35 to 0.85; P = 0.007). In patients with respiratory distress syndrome, NMBAs may be beneficial in reverse refractory hypoxemia and may be associated with reduced short-term mortality and incidence of barotrauma. However, there is no significant effects of NMBAs on mid-term and long-term mortality, and further studies are required.

    更新日期:2020-01-13
  • Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-13
    Zhihui Wu; Qiang Gong; Yan Yu; Jialin Zhu; Wencan Li

    Due to the acquired drug resistance, the potency of cisplatin-based chemotherapy is limited in lung cancer, which is a big obstacle in clinical treatment of lung cancer. Abundant evidence has revealed that circular RNAs (circRNAs) exerted facilitating or suppressive function on the tumorigenesis of multiple cancers. The oncogenic role of circ-ABCB10 in breast cancer and clear cell renal cell carcinoma has been validated in recent researches. However, the regulatory mechanism of circ-ABCB10 and its relation to cellular sensitivity to cisplatin in lung cancer is poorly understood. The expression and characteristic of circ-ABCB10 were analyzed by RT-qPCR and nucleic acid electrophoresis. CCK-8, colony formation, TUNEL and transwell assays were applied to probe the role of FOXD3-AS1 in lung cancer. The interactions of miR-556-3p with circ-ABCB10 and AK4 were testified by luciferase reporter and RIP assays. Circ-ABCB10 was markedly upregulated and featured with loop structure in lung cancer. Circ-ABCB10 depletion suppresses lung cancer progression and sensitizes lung cancer cells to cisplatin. Molecular mechanism assays manifested that circ-ABCB10 bound with miR-556-3p and negatively modulated miR-556-3p expression. Additionally, AK4 was testified to be the downstream target of miR-556-3p. More importantly, rescue assays clarified that upregulation of AK4 could reverse the cisplatin-sensitizing and tumor-suppressing effect of circ-ABCB10 knockdown on lung cancer cells. Circ-ABCB10 knockdown enhances sensitivity of lung cancer cells to cisplatin by targeting miR-556-3p/AK4 axis.

    更新日期:2020-01-13
  • 更新日期:2020-01-13
  • Impact of diffusing lung capacity before and after neoadjuvant concurrent chemoradiation on postoperative pulmonary complications among patients with stage IIIA/N2 non-small-cell lung cancer
    Respir. Res. (IF 3.829) Pub Date : 2020-01-10
    Sumin Shin; Yong Soo Choi; Jae Jun Jung; Yunjoo Im; Sun Hye Shin; Danbee Kang; Jong Ho Cho; Hong Kwan Kim; Jhingook Kim; Jae Ill Zo; Young Mog Shim; Keunchil Park; Myung-Ju Ahn; Yong Chan Ahn; Genehee Lee; Juhee Cho; Ho Yun Lee; Hye Yun Park

    This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco < 80% predicted and DLco < 60% predicted, respectively. On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36–3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68–8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.

    更新日期:2020-01-11
  • Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs
    Respir. Res. (IF 3.829) Pub Date : 2020-01-10
    Yifang Liao; Ping Li; Yanxia Wang; Hong Chen; Shangwei Ning; Dongju Su

    Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.

    更新日期:2020-01-11
  • The stability of blood Eosinophils in chronic obstructive pulmonary disease
    Respir. Res. (IF 3.829) Pub Date : 2020-01-10
    Gabriella H. Long; Thomas Southworth; Umme Kolsum; Gavin C. Donaldson; Jadwiga A. Wedzicha; Christopher E. Brightling; Dave Singh

    Blood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD). We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort. Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year. 85.3% of patients with eosinophils < 100 cells/μL had stable counts. The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds.

    更新日期:2020-01-11
  • Lung-protective ventilation worsens ventilator-induced diaphragm atrophy and weakness
    Respir. Res. (IF 3.829) Pub Date : 2020-01-10
    Xian-Long Zhou; Xiao-Jun Wei; Shao-Ping Li; Hao-Li Ma; Yan Zhao

    Lung–protective ventilation (LPV) has been found to minimize the risk of ventilator–induced lung injury (VILI). However, whether LPV is able to diminish ventilator–induced diaphragm dysfunction (VIDD) remains unknown. This study was designed to test the hypothesis that LPV protects the diaphragm against VIDD. Adult male Wistar rats received either conventional mechanical (tidal volume [VT]: 10 ml/kg, positive end–expiratory pressure [PEEP]: 2 cm H2O; CV group) or lung-protective (VT: 5 ml/kg, PEEP: 10 cm H2O; LPV group) ventilation for 12 h. Then, diaphragms and lungs were collected for biochemical and histological analyses. Transcriptome sequencing (RNA–seq) was performed to determine the differentially expressed genes in the diaphragms between groups. Our results suggested that LPV was associated with diminished pulmonary injuries and reduced oxidative stress compared with the effects of the CV strategy in rats. However, animals that received LPV showed increased protein degradation, decreased cross–sectional areas (CSAs) of myofibers, and reduced forces of the diaphragm compared with the same parameters in animals receiving CV (p < 0.05). In addition, the LPV group showed a higher level of oxidative stress in the diaphragm than the CV group (p < 0.05). Moreover, RNA–seq and western blots revealed that the peroxisome proliferator–activated receptor γ coactivator–1alpha (PGC–1α), a powerful reactive oxygen species (ROS) inhibitor, was significantly downregulated in the LPV group compared with its expression in the CV group (p < 0.05). Compared with the CV strategy, the LPV strategy did not protect the diaphragm against VIDD in rats. In contrast, the LPV strategy worsened VIDD by inducing oxidative stress together with the downregulation of PGC–1α in the diaphragm. However, further studies are required to determine the roles of PGC–1α in ventilator-induced diaphragmatic oxidative stress.

    更新日期:2020-01-11
  • Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
    Respir. Res. (IF 3.829) Pub Date : 2020-01-10
    Mona Bafadhel; Dave Singh; Christine Jenkins; Stefan Peterson; Thomas Bengtsson; Peter Wessman; Malin Fagerås

    Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69–84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.

    更新日期:2020-01-11
  • Age-specific incidence of allergic and non-allergic asthma
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-10
    Johanna Pakkasela; Pinja Ilmarinen; Jasmin Honkamäki; Leena E. Tuomisto; Heidi Andersén; Päivi Piirilä; Hanna Hisinger-Mölkänen; Anssi Sovijärvi; Helena Backman; Bo Lundbäck; Eva Rönmark; Hannu Kankaanranta; Lauri Lehtimäki

    Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. Questionnaires were sent to 8000 randomly selected recipients aged 20–69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0–9, 10–19, 20–29, 30–39, 40–49, 50–59 and 60–69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50–59 years old). The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.

    更新日期:2020-01-11
  • Comorbidities and survival in patients with chronic hypersensitivity pneumonitis
    Respir. Res. (IF 3.829) Pub Date : 2020-01-09
    Julia Wälscher; Benjamin Gross; Julie Morisset; Kerri A. Johannson; Martina Vasakova; Jacques Bruhwyler; Michael Kreuter

    Chronic Hypersensitivity Pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from repeated exposure to an offending antigen. Prognostication in cHP remains challenging, and the relationship between comorbidities and survival has yet to be characterized. The aim of this study was to describe the relationship between comorbid conditions and survival in patients with cHP. The prospective database from a tertiary referral centre for ILD was reviewed for patient-reported comorbidities, their frequency, and relationship with survival in cHP patients. Comorbidities were assessed by direct questioning of the patient at the baseline visit and by a standardized questionnaire for the diagnosis of interstitial lung diseases. During the follow-up examinations, patients were asked about newly diagnosed comorbidities. Two hundred eleven patients with cHP were identified (mean age 63 years, 53% male, mean FVC 73%), with mean follow-up of 32 months. The mean number of comorbidities was 3 (10% had 0, 59% 1–3 and 31% ≥4 comorbidities). Most frequent comorbidities groups were cardiovascular (65%) and respiratory (26%), most common comorbidities were hypertension (56%), gastro-esophageal reflux disease (GERD) (24%), diabetes (20%) and coronary heart disease (18%). In general, deceased patients had more comorbidities than survivors (p = 0.005), yet there was no association between the absolute number of comorbidities and survival. Pulmonary hypertension (30.8% versus 5.7%, p = 0.001;), diastolic dysfunction (26.9% versus 6.4%, p = 0.004) and cerebrovascular disease were more frequent in non-survivors (23.1% versus 7.6%, p = 0.026). Lung cancer was not observed, and neither GERD nor antacid drugs were associated with outcome (p = 0.357 and p = 0.961, respectively). Comorbidities are common in cHP are associated with survival. Further work should determine whether interventions for these specific comorbidities can positively affect survival.

    更新日期:2020-01-09
  • The value of serum Krebs von den lungen-6 as a diagnostic marker in connective tissue disease associated with interstitial lung disease
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-08
    Hua Ma; Junhui Lu; Yuanyuan Song; Huixuan Wang; Songlou Yin

    The purpose of this study was to evaluate the value of serum krebs von den lungen-6 (KL-6) level as a diagnostic indicator for connective tissue disease associated with interstitial lung disease (CTD-ILD). One hundred fifty five patients with newly diagnosed CTD in our hospital were enrolled and divided into two groups by their ILD manifestations, the CTD-ILD group and the CTD group. In parallel, 61 patients with pulmonary infection and 60 cases of healthy subjects were also enrolled into the study. The difference of serum KL-6 level among the four groups were compared. In CTD-ILD group, carbon monoxide diffusing capacity (DLCo) and high-resolution computed tomography (HRCT) of lung were also tested. The serum KL-6 level of 32 patients from the CTD-ILD group who received cyclophosphamide (CTX) pulse therapy were sampled and measured, by enzyme linked immunosorbent assay (ELISA), at three time points: before treatment, 3 months after treatment and 6 months after treatment. The serum KL-6 level in the CTD-ILD group (1004.9 (676.41738.1) IU/ml) is significantly higher than three other groups (χ2 = 72.29, P < 0.001). In the CTD-ILD group the level of serum KL-6 was positively correlated with disease severity on HRCT (r = 0.75, P < 0.001), while was negatively correlated with DLCo (r = − 0.50, P < 0.001). In 32 patients who received CTX pulse therapy, the level of serum KL-6 was gradually decreased in 20 cases whose lesions were absorbed within 6 months (F = 13.67, P < 0.001), whereas it remained unchanged in the rest of 12 patients (Z = -1.328, P = 0.198). Serum KL-6 level can potentially serve as a diagnostic marker for CTD-ILD and be utilized to evaluate the effectiveness of CTX pulse therapy.

    更新日期:2020-01-09
  • A multicentre prospective observational study comparing arterial blood gas values to those obtained by pulse oximeters used in adult patients attending Australian and New Zealand hospitals
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-09
    Janine Pilcher; Laura Ploen; Steve McKinstry; George Bardsley; Jimmy Chien; Lesley Howard; Sharon Lee; Lutz Beckert; Maureen Swanney; Mark Weatherall; Richard Beasley

    Pulse oximetry is widely used in the clinical setting. The purpose of this validation study was to investigate the level of agreement between oxygen saturations measured by pulse oximeter (SpO2) and arterial blood gas (SaO2) in a range of oximeters in clinical use in Australia and New Zealand. Paired SpO2 and SaO2 measurements were collected from 400 patients in one Australian and two New Zealand hospitals. The ages of the patients ranged from 18 to 95 years. Bias and limits of agreement were estimated. Sensitivity and specificity for detecting hypoxaemia, defined as SaO2 < 90%, were also estimated. The majority of participants were recruited from the Outpatient, Ward or High Dependency Unit setting. Bias, oximeter-measured minus arterial blood gas-measured oxygen saturation, was − 1.2%, with limits of agreement − 4.4 to 2.0%. SpO2 was at least 4% lower than SaO2 for 10 (2.5%) of the participants and SpO2 was at least 4% higher than the SaO2 in 3 (0.8%) of the participants. None of the participants with a SpO2 ≥ 92% were hypoxaemic, defined as SaO2 < 90%. There were no clinically significant differences in oximetry accuracy in relation to clinical characteristics or oximeter brand. In the majority of the participants, pulse oximetry was an accurate method to assess SaO2 and had good performance in detecting hypoxaemia. However, in a small proportion of participants, differences between SaO2 and SpO2 could have clinical relevance in terms of patient monitoring and management. A SpO2 ≥ 92% indicates that hypoxaemia, defined as a SaO2 < 90%, is not present. Australian and New Zealand Clinical Trials Registry (ACTRN12614001257651). Date of registration: 2/12/2014.

    更新日期:2020-01-09
  • Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-09
    Mazen Kreidy; Ali Al-Hilli; Ralph Yachoui; Jeffrey Resnick

    Scleromyxedema is a progressive, systemic connective tissue disorder characterized by fibro-mucous skin lesions and increased serum monoclonal immunoglobulin levels. Pulmonary involvement occurs in a subset of patients, though the overall prevalence of pulmonary lesions in scleromyxedema is unknown. Since pulmonary hypertension presumably occurs in these patients due to disease progression and development of additional conditions, treatment of the underlying plasma cell dyscrasia and connective tissue disorder may improve pulmonary hypertension symptoms. An elderly patient with scleromyxedema developed pulmonary hypertension refractory to vasodilator and diuretic therapy and subsequently multiple myeloma that responded to a combination therapy of bortezomib, cyclophosphamide, and dexamethasone treatment. Treatment of the underlying disease(s) that contributed to pulmonary hypertension development with anti-neoplastic agents like bortezomib may improve cardiopulmonary symptoms secondary to reducing abnormal blood cell counts and paraprotein levels.

    更新日期:2020-01-09
  • ICS-formoterol reliever therapy stepwise treatment algorithm for adult asthma
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Richard Beasley; Irene Braithwaite; Alex Semprini; Ciléin Kearns; Mark Weatherall; Tim W. Harrison; Alberto Papi; Ian D. Pavord

    A stepwise approach to the pharmacological treatment of asthma is a key feature of current asthma guidelines [1–4]. Through algorithms, treatment intensity is “stepped up” to obtain asthma control and reduce the risk of exacerbations, and “stepped down” after a period of prolonged control and absence of exacerbations. Traditional algorithms advocated short-acting β2-agonist (SABA) reliever therapy for all levels of severity, initially as sole therapy at Step 1, together with maintenance “low dose” inhaled corticosteroids (ICS) at Step 2, with maintenance ICS/long-acting β2-agonist (LABA) at “low”, “moderate” or “high” doses at Steps 3 and 4, and finally with “add-on” therapies at Step 5. A practical “anti-inflammatory reliever therapy”-based algorithm based on the GINA 2019 update is presented, together with a prototype action plan to facilitate its implementation.

    更新日期:2020-01-09
  • Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Peter R. Eastwood; Maree Barnes; Stuart G. MacKay; John R. Wheatley; David R. Hillman; Xuân-Lan Nguyên; Richard Lewis; Matthew C. Campbell; Boris Pételle; Jennifer H. Walsh; Andrew C. Jones; Carsten E. Palme; Alain Bizon; Nicole Meslier; Chloé Bertolus; Kathleen J. Maddison; Laurent Laccourreye; Guillaume Raux; Katleen Denoncin; Valérie Attali; Frédéric Gagnadoux; Sandrine H. Launois

    Background and aim Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. Methods This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea–hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number [NCT03048604][1]. Results 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m−2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h−1, a mean change of 10.8 events·h−1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h−1, a mean change of 9.3 events·h−1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. Conclusions Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm. A new method of hypoglossal nerve stimulation to treat sleep apnoea does so bilaterally via an implanted neurostimulator activated externally. Its simplicity and relative non-invasiveness have not compromised its effectiveness relative to older methods. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03048604&atom=%2Ferj%2F55%2F1%2F1901320.atom

    更新日期:2020-01-09
  • Characteristics and treatment regimens across ERS SHARP severe asthma registries
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Job J.M.H. van Bragt; Ian M. Adcock; Elisabeth H.D. Bel; Gert-Jan Braunstahl; Anneke ten Brinke; John Busby; Giorgio W. Canonica; Hui Cao; Kian Fan Chung; Zsuzsanna Csoma; Barbro Dahlén; Elizabeth Davin; Susanne Hansen; Enrico Heffler; Ildiko Horvath; Stephanie Korn; Maxim Kots; Piotr Kuna; Namhee Kwon; Renaud Louis; Vicente Plaza; Celeste Porsbjerg; David Ramos-Barbon; Levi B. Richards; Sabina Škrgat; Jacob K. Sont; Susanne J.H. Vijverberg; Els J.M. Weersink; Valentyna Yasinska; Scott S. Wagers; Ratko Djukanovic; Anke H. Maitland-van der Zee

    Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals. This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases. Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively. The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries. The severe asthma population in Europe is heterogeneous and differs in clinical characteristics and treatment. Harmonisation across registries and guidelines is needed and requires collection of same data across cohorts to enable future research in SHARP.

    更新日期:2020-01-09
  • Systems biology and big data in asthma and allergy: recent discoveries and emerging challenges
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Howard H.F. Tang; Peter D. Sly; Patrick G. Holt; Kathryn E. Holt; Michael Inouye

    Asthma is a common condition caused by immune and respiratory dysfunction, and it is often linked to allergy. A systems perspective may prove helpful in unravelling the complexity of asthma and allergy. Our aim is to give an overview of systems biology approaches used in allergy and asthma research. Specifically, we describe recent “omic”-level findings, and examine how these findings have been systematically integrated to generate further insight. Current research suggests that allergy is driven by genetic and epigenetic factors, in concert with environmental factors such as microbiome and diet, leading to early-life disturbance in immunological development and disruption of balance within key immuno-inflammatory pathways. Variation in inherited susceptibility and exposures causes heterogeneity in manifestations of asthma and other allergic diseases. Machine learning approaches are being used to explore this heterogeneity, and to probe the pathophysiological patterns or “endotypes” that correlate with subphenotypes of asthma and allergy. Mathematical models are being built based on genomic, transcriptomic and proteomic data to predict or discriminate disease phenotypes, and to describe the biomolecular networks behind asthma. The use of systems biology in allergy and asthma research is rapidly growing, and has so far yielded fruitful results. However, the scale and multidisciplinary nature of this research means that it is accompanied by new challenges. Ultimately, it is hoped that systems medicine, with its integration of omics data into clinical practice, can pave the way to more precise, personalised and effective management of asthma. With the recent influx of “big data” in asthma research, clinicians and scientists need to become familiar with analytical approaches that use systems-based methods to make sense of large datasets

    更新日期:2020-01-09
  • Obstructive sleep apnoea severity and liver steatosis measured by magnetic resonance imaging
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Wojciech Trzepizur; Jérôme Boursier; Anna Berréhare; Marc Le Vaillant; Ramaroson Andriantsitohaina; Pierre-Henri Ducluzeau; Séverine Dubois; Samir Henni; Pierre Abraham; Paul Calès; Christophe Aubé; Anita Paisant; Frédéric Gagnadoux

    Obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease (NAFLD) are two of many diseases associated with obesity. NAFLD is a common condition ranging in severity from liver steatosis to non-alcoholic steatohepatitis and liver fibrosis, the last step of NAFLD progression. Numerous studies have investigated whether the frequent co-occurrence of OSA and NAFLD simply reflects their link to obesity, or whether there is an independent pathophysiological interconnection between the two diseases (see [1] for comprehensive review). In animal models, intermittent hypoxia mimicking OSA has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, liver steatosis and fibrosis [1]. In patients with OSA and metabolic comorbidities, liver steatosis measured by magnetic resonance imaging is associated with male sex and insulin resistance, but not with OSA severity and nocturnal hypoxia The METABOL Group: Département de Pneumologie, CHU, Angers, France: Nicole Meslier, Pascaline Priou; Service d'Hépato-gastroentérologie, CHU, Angers, France: Frédéric Oberti, Isabelle Fouchard-Hubert, Adrien Lannes, Sandra Girres; Département d'Endocrinologie, Diabétologie, Nutrition, CHU, Angers, France: Ingrid Allix; Département de Médecine du Sport et Explorations Fonctionnelles Vasculaires, CHU, Angers, France: Georges Leftheriotis; INSERM UMR 1063 “SOPAM”, Univeristé d'Angers, Angers, France: Carmen Martinez, Soazig Le Lay, Raffaella Soleti, Luisa Vergori; Département de la Recherche Clinique et Innovation, CHU, Angers, France: Jean-Marie Chrétien; Centre de Resource Biologique, CHU, Angers, France: Odile Blanchet, Belaid Sekour; Laboratoire HIFIH, EA3859, Université d'Angers, France: Gilles Hunault.

    更新日期:2020-01-09
  • Latent tuberculosis infection among minor asylum seekers in Denmark
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Banoo Bakir Ahmad; Kristina Langholz Kristensen; Jonathan Peter Glenthoej; Anja Poulsen; Ann-Gine Bryld; Franziska Grundtvig Huber; Ebbe Munk Andersen; Pernille Ravn

    We read with interest the study by Wolters et al . [1], reporting the results of radiographic tuberculosis (TB) entry screening of asylum seekers in the Netherlands. We agree with the authors that we lack sufficient studies concerning latent TB infection (LTBI) screening among minor asylum seekers, and we present our study investigating LTBI prevalence and the coverage of follow-up in terms of clinical evaluation and treatment of LTBI among minor asylum seekers arriving in Denmark. Screening among minor asylum seekers in Denmark revealed a high LTBI prevalence with heterogeneity in terms of clinical evaluation and initiating preventive treatment, underlining the need for uniform management of LTBI screening and treatment

    更新日期:2020-01-09
  • Long-term effect of CFTR modulator therapy on airway nitric oxide
    Eur. Respir. J. (IF 11.807) Pub Date : 2020-01-01
    Hartmut Grasemann; Michelle Klingel; Julie Avolio; Carley Prentice; Tanja Gonska; Elizabeth Tullis; Felix Ratjen

    The fraction of exhaled nitric oxide ( F eNO) is generally lower in individuals with cystic fibrosis (CF), compared to healthy controls. Two recent studies reported that the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator ivacaftor resulted in an increase in F eNO after 4 weeks’ therapy [1, 2], suggesting that changes in F eNO have the potential to serve as biomarker of restored CFTR function. Ivacaftor results in a sustained increase in F eNO in children and adults with CF. The increase in F eNO may be related to changes in airway NO metabolism by myeloperoxidase. Lumacaftor–ivacaftor therapy does not have an immediate effect on F eNO. We thank all patients and families who participated in this research study. Mass spectrometry analyses were performed at the Analytical Facility for Bioactive Molecules (AFBM) of the Centre for the Study of Complex Childhood Diseases (CSCCD) at the Hospital for Sick Children (Toronto, ON, Canada). The CSCCD was supported by the Canadian Foundation for Innovation (CFI).

    更新日期:2020-01-09
  • SOD2 ameliorates pulmonary hypertension in a murine model of sleep apnea via suppressing expression of NLRP3 in CD11b+ cells
    Respir. Res. (IF 3.829) Pub Date : 2020-01-08
    Cuiping Fu; Shengyu Hao; Zilong Liu; Liang Xie; Xu Wu; Xiaodan Wu; Shanqun Li

    High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mechanism of CIH induced PH is not clear. One of the molecules that plays a key role in regulating pulmonary artery function under hypoxic conditions is superoxide dismutase 2 (SOD2). Our study utilized heterozygous SOD2−/+ mice firstly in CIH model to explore the exact role of SOD2 in CIH causing PH. Expression of SOD2 was analyzed in CIH model. Echocardiography and pulmonary hypertension were measured in wild type (WT) and SOD2−/+ mice under normal air or CIH condition. Hematoxylin–Eosin (H&E) staining and masson staining were carried out to evaluate pulmonary vascular muscularization and remodeling. Micro-PET scanning of in vivo 99mTc-labelled- MAG3-anti-CD11b was applied to assess CD11b in quantification and localization. Level of nod-like receptor pyrin domain containing 3 (NLRP3) was analyzed by real time PCR and immunohistochemistry (IHC). Results showed that SOD2 was down-regulated in OSA/CIH model. Deficiency of SOD2 aggravated CIH induced pulmonary hypertension and pulmonary vascular hypertrophy. CD11b+ cells, especially monocytic myeloid cell line-Ly6C+Ly6G− cells, were increased in the lung, bone marrow and the blood under CIH condition, and down-regulated SOD2 activated NLRP3 in CD11b+ cells. SOD2-deficient-CD11b+ myeloid cells promoted the apoptosis resistance and over-proliferation of human pulmonary artery smooth muscle cells (PASMCs) via up-regulating NLRP3. CIH induced down-regulating of SOD2 increased pulmonary hypertension and vascular muscularization. It could be one of the mechanism of CIH leading to PH.

    更新日期:2020-01-08
  • Characteristic chest CT findings for progressive cavities in Mycobacterium avium complex pulmonary disease: a retrospective cohort study
    Respir. Res. (IF 3.829) Pub Date : 2020-01-08
    Yohei Oshitani; Seigo Kitada; Ryuya Edahiro; Kazuyuki Tsujino; Hiroyuki Kagawa; Kenji Yoshimura; Keisuke Miki; Mari Miki; Hiroshi Kida

    Although cavities are an important finding in Mycobacterium avium complex pulmonary disease (MAC-PD), there is little information regarding the types of cavities that indicate disease progression. This study was performed to identify cavity characteristics that were associated with disease progression in patients with MAC-PD. This retrospective cohort study included 97 patients presenting with MAC-PD with cavities between December 2006 and June 2016. We compared initial and final computed tomography (CT) findings, classified 52 and 45 patients in the progressive and non-progressive cavity groups, respectively, and examined the progression-related imaging features in initial CT images. A progressive cavity was defined by more than two-fold increase in internal diameter or emergence of a new cavity around the initial cavity. Patients in the progressive group were older (p < 0.001), had a lower body mass index (p = 0.043), and showed higher diabetes complication rates (p = 0.005). The initial CT in the progressive group showed a longer maximum internal diameter of the cavity (p < 0.001) and higher rates of cavities close to the chest wall (p < 0.001), multiple cavities (p = 0.023), consolidation around the cavity (p < 0.001), atelectasis (p = 0.011), and pleural thickening (p < 0.001). Multivariable logistic regression analysis revealed that the maximum internal diameter of the cavity (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.02–1.21; p=0.012) and consolidation around the cavity (OR: 16.15, 95% CI: 4.05–64.46; p < 0.001) were significantly associated with progressive cavities. In cavities with a maximum internal diameter of ≥10 mm and simultaneous consolidation, the probability of progression was as high as 96.2%. The 10-year mortality rates in the progressive and non-progressive cavity groups were 46.7 and 9.8% (p < 0.001), respectively, while the 10-year respiratory failure rates were 28.1 and 0%, respectively (p < 0.001). Large cavity size and consolidation on CT showed strong relationships with disease progression, which led to respiratory failure and high mortality rate.

    更新日期:2020-01-08
  • The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis
    Respir. Res. (IF 3.829) Pub Date : 2020-01-08
    Tanja Tran; Martina Šterclová; Nesrin Mogulkoc; Katarzyna Lewandowska; Veronika Müller; Marta Hájková; Mordechai R. Kramer; Dragana Jovanović; Jasna Tekavec-Trkanjec; Michael Studnicka; Natalia Stoeva; Karel Hejduk; Ladislav Dušek; Samy Suissa; Martina Vašáková

    Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3–3.7) and III (HR 4.0; 95% CI: 2.8–5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8–4.0) and 5.8 (95% CI: 4.0–8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5–2.9) and lung cancer (HR 2.6; 95% CI: 1.3–4.9). EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.

    更新日期:2020-01-08
  • A systematic review with meta-analysis of gastroesophageal reflux disease and exacerbations of chronic obstructive pulmonary disease
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-08
    Chunrong Huang; Yahui Liu; Guochao Shi

    Gastroesophageal reflux disease (GERD) was suggested to be associated with exacerbations of chronic obstructive pulmonary disease (COPD) in recent years. The aim of this study was to examine the association between GERD and COPD exacerbation through a meta-analysis. Databases including EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched with a systematic searching strategy for original articles, published until Jan 2019, without language restriction. A total of 13,245 patients from 10 observational articles were included in the meta-analysis. The meta-analysis indicated that GERD is associated with increased risk of COPD exacerbation (OR: 5.37; 95% CI 2.71–10.64). Patients with COPD and GERD had increased number of exacerbation (WMD: 0.48; 95% CI: 0.31 to 0.65). The meta-analysis showed that there was a significant correlation between GERD and COPD exacerbation.

    更新日期:2020-01-08
  • Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-08
    Luca Richeldi; Martin Kolb; Stéphane Jouneau; Wim A. Wuyts; Birgit Schinzel; Susanne Stowasser; Manuel Quaresma; Ganesh Raghu

    The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30–79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline. Analyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive. In total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were − 52.3 and − 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and − 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS. Based on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease. INPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).

    更新日期:2020-01-08
  • A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-08
    Yuki Yabuuchi; Hitomi Goto; Mizu Nonaka; Hiroaki Tachi; Tatsuya Akiyama; Naoki Arai; Hiroaki Ishikawa; Kentaro Hyodo; Kenji Nemoto; Yukiko Miura; Isano Hase; Shingo Usui; Shuji Oh-ishi; Kenji Hayashihara; Takefumi Saito; Tatsuya Chonan

    Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

    更新日期:2020-01-08
  • Co-infection with Streptococcus anginosus and Mycobacterium tuberculosis in an immunocompetent pediatric patient. A case report
    BMC Pulm. Med. (IF 2.184) Pub Date : 2020-01-08
    Napoleon González Saldaña; José Iván Castillo Bejarano; Marte Hernández Porras; Eduardo Arias de la Garza; Sofia Fortes Gutiérrez; Jose Luis Copado Gutiérrez; Hugo Juarez Olguin

    Simultaneous infection in tuberculosis (TB) is rare. The mixed infection between Streptococcus anginosus group (SAG) and M. tuberculosis (MTB) has not been reported in children. The aim of this report was to describe a pediatric case with a pulmonary abscess caused by the duality SAG-MTB co-infection. An 11-year-old boy with an acute onset of throbbing pain of two-day evolution located in the anterior chest wall. The patient reported a history of fever, cough and rhinorrhea during the last seven days. An anterior chest radiography revealed a heterogenic opacity at the lower right lobe while the lateral projection showed an obliteration at the anterior diaphragmatic insertion. Parenteral Ceftriaxone (100 mg/kg/day) and Dicloxacillin (200 mg/kg/day) was started. The abscess was subsequently drained and analyzed. After a year of follow-up, the patient remained asymptomatic. This case represents the first reported case of pulmonary co-infection involving MTB and SAG in an immunocompetent pediatric patient.

    更新日期:2020-01-08
  • Mendelian randomisation supports causal link between obesity and asthma
    Thorax (IF 9.640) Pub Date : 2020-01-08
    Diana A van der Plaat

    Over the last few decades the prevalence of both obesity and asthma has increased substantially in many parts of the world. A clear link between obesity and asthma incidence and severity has been shown in both children and adults in observational studies.1 2 The biological mechanisms underlying this relationship are not fully understood. Hypotheses to explain the association include mechanisms related to one or more factors, including systemic inflammation, endocrine factors, oxidative stress, decreased lung volumes and comorbidities (type 2 diabetes, obstructive sleep apnoea and gastro-oesophageal reflux disease).3–6 The systemic inflammation pathway has gained particular traction, as both obese subjects and asthmatics have high inflammatory burdens. In addition, obese patients with asthma present with a different type of airway inflammation, tending to be more neutrophilic than eosinophilic.3 Controversy exists over whether obesity has a different effect on asthma in males and females, as studies in children show mixed results while some studies in adults suggest stronger effects in females.4 5 Furthermore, there has been a concern that the body mass index (BMI)–asthma association is due to reverse causation; that is, that people with asthma become obese due to the impact of asthma on their ability to remain active or perhaps even due to medications. Overall, findings by observational studies are susceptible to bias (confounding) and cannot elucidate the directionality of the relationship between obesity and asthma. The Mendelian randomisation (MR) approach is increasingly used to assess causal relationships and can be regarded as a ‘natural’ randomised controlled trial. MR uses genetic variants (single nucleotide polymorphisms; SNP), which were randomly assigned at conception, as proxies (‘instrumental variables’) for an exposure of interest.7 Indirect evidence of a causal effect of the exposure on the outcome is provided when the SNPs that are known to modify the exposure …

    更新日期:2020-01-08
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