Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 532
Filtrar
1.
Int J Chron Obstruct Pulmon Dis ; 15: 2787-2798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177816

RESUMO

Background: Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD. Methods: We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1-4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models. Results: Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22-0.98). Conclusion: Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients' socioeconomic factors are relevant and should be taken into account by clinicians.

2.
J Immunol ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158955

RESUMO

Macrophage-inducible C-type lectin (Mincle)-dependent sensing of pathogens triggers proinflammatory immune responses in professional phagocytes that contribute to protecting the host against pathogen invasion. In this study, we examined whether overexpression of Mincle that is designed to improve early pathogen sensing by professional phagocytes would improve lung-protective immunity against Streptococcus pneumoniae in mice. Proteomic profiling of alveolar macrophages of Mincle transgenic (tg) mice stimulated with the Mincle-specific pneumococcal ligand glucosyl-diacylglycerol (Glc-DAG) revealed increased Nlrp3 inflammasome activation and downstream IL-1ß cytokine release that was not observed in Glc-DAG-stimulated Mincle knockout or Nlrp3 knockout macrophages. Along this line, Mincle tg mice also responded with a stronger Nlrp3 expression and early proinflammatory cytokine release after challenge with S. pneumoniae, ultimately leading to fatal pneumonia in the Mincle tg mice. Importantly, Nlrp3 inhibitor treatment of Mincle tg mice significantly mitigated the observed hyperinflammatory response to pneumococcal challenge. Together, we show that overexpression of the pattern recognition receptor Mincle triggers increased Glc-DAG-dependent Nlrp3 inflammasome activation in professional phagocytes leading to fatal pneumococcal pneumonia in mice that is amenable to Nlrp3 inhibitor treatment. These data show that ectopic expression of the Mincle receptor confers increased susceptibility rather than resistance to S. pneumoniae in mice, thus highlighting the importance of an inducible Mincle receptor expression in response to microbial challenge.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33171069

RESUMO

Rationale: The Global Burden of Disease programme identified smoking, and ambient and household air pollution as the main drivers of death and disability from Chronic Obstructive Pulmonary Disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a post-bronchodilator one-second forced expiratory volume to forced vital capacity ratio < lower limit of normal, and the relative risks associated with different risk factors. Local RR were estimated using a Bayesian hierarchical model borrowing information from across sites. From these RR and the prevalence of risk factors, we estimated local Population Attributable Risks (PAR). Measurements and Main Results: Mean prevalence of CAO was 11.2% in men and 8.6% in women. Mean PAR for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index (BMI), and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: While smoking remains the most important risk factor for CAO, in some areas poor education, low BMI and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

4.
BMJ Open Respir Res ; 7(1)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33020115

RESUMO

BACKGROUND: Nasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and CFTR genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD). METHODS: NPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group. RESULTS: We assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and CFTR genetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with a CFTR genotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identified CFTR mutation. If two CFTR sequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range. CONCLUSION: The majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-type CFTR coding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region of CFTR or elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.

5.
J Intensive Care Med ; : 885066620965169, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063613

RESUMO

BACKGROUND: Deficiency of immunoglobulins of the classes IgG, IgG1, IgA and IgM is associated with severity of disease and mortality in sepsis and septic shock. Therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) has recently gained attention as an adjunctive therapeutic option in early septic shock. We hypothesized that TPE might modulate immunoglobulin deficiencies besides sole elimination of circulating injurious molecules. METHODS: We conducted a prospective single center study with TPE in 33 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4µg/kg/min). Clinical and biochemical data, including measurement of immunoglobulin subgroups IgG, IgG1, IgM and IgA were obtained before and after TPE. The following immunoglobulin cut-off values were used to analyze subgroups with low immunoglobulin concentrations at baseline (IgG ≤ 6.5, IgG1 ≤ 3, IgM ≤ 1.5 and IgA ≤ 0.35 g/L). RESULTS: At inclusion, median (IQR) SOFA score was 18 (15-20) and NE dose was 0.8 (0.6-1.2) µg/kg/min. The majority of patients demonstrated profound reductions in immunoglobulins levels of all classes. Globally, immunoglobulin levels were not significantly changed after a single TPE session. However, in patients with low baseline immunoglobulin levels a significant increase in all classes was observed (IgG 1.92 (0.96-3) g/L (+41%), IgG1 2.1 (1.46-2.32) g/L (+96%), IgA 0.44 (0.12-0.62) g/L (59%) and IgM 0.18 (0.14-0.34) g/L (+55%), p < 0.001 for comparison to patients above cut-off). CONCLUSIONS: The majority of early and severe septic shock patients had reduced immunoglobulin levels and a single TPE could attenuate immunoglobulin deficiencies of all classes. The clinical relevance of this observation has to be investigated in a proper designed trial.

6.
Dtsch Arztebl Int ; 117(31-32): 528-533, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32900426

RESUMO

BACKGROUND: The reported high mortality of COVID-19 patients in intensive care has given rise to a debate over whether patients with this disease are being intubated too soon and might instead benefit from more non-invasive ventilation. METHODS: This review is based on articles published up to 12 June 2020 that were retrieved by a selective literature search on the topic of invasive and non-invasive ventilation for respiratory failure in COVID-19. Guideline recommendations and study data on patients with respiratory failure in settings other than COVID-19 are also considered, as are the current figures of the intensive care registry of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin). RESULTS: The high mortality figures among patients receiving invasive ventilation that have been reported in studies from abroad cannot be uncritically applied to the current situation in Germany. Study data on ventilation specifically in COVID-19 patients would be needed to do justice to the special pathophysiology of this disease, but such data are lacking. Being intubated too early is evidently associated with risks for the patient, but being intubated too late is as well. A particularly im - portant consideration is the potential harm associated with prolonged spontaneous breathing, with or without non-invasive assistance, as any increase in respiratory work can seriously worsen respiratory failure. On the other hand, it is clearly unacceptable to intubate patients too early merely out of concern that the medical staff might become infected with COVID-19 if they were ventilated non-invasively. CONCLUSION: Nasal high flow, non-invasive ventilation, and invasive ventilation with intubation should be carried out in a stepwise treatment strategy, under appropriate intensive-care monitoring and with the observance of all relevant anti-infectious precautions. Germany is better prepared that other countries to provide COVID-19 patients with appropriate respiratory care, in view of the high per capita density of intensive-care beds and the availability of a nationwide, interdisciplinary intensive care registry for the guidance and coordination of intensive care in patients who need it.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Infecções por Coronavirus/epidemiologia , Alemanha/epidemiologia , Humanos , Ventilação não Invasiva , Pandemias , Pneumonia Viral/epidemiologia
7.
Chest ; 158(3): e127-e132, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32892889

RESUMO

CASE PRESENTATION: A 37-year-old previously healthy and athletic woman presented to the ED in October 2018 with acute-onset high fever, dyspnea, and productive cough. Chest radiograph showed bilateral infiltrates that correlated with multifocal ground glass opacities in a thoracic CT scan (Fig 1). The patient was severely hypoxemic and required intensive care and oxygen administration via a high-flow nasal cannula. On admission, leucocyte counts were 23.3 k/µL; platelet counts were 518 k/µL; hemoglobin level was 12 g/dL; C-reactive protein was 83 mg/L, and procalcitonin was 0.7 µg/L. An auto-antibody panel that included antinuclear antibodies, extractable nuclear antigen (including anti-centromere-antibodies), antineutrophil cytoplasmic antibodies, and myositis- and granulocyte macrophage colony-stimulating factor-antibodies was negative, as was the rheumatoid factor. Immunoglobulins that included IgG1-4 and IgA and renal function were normal. Sicca symptoms like xerophthalmia and xerostomia were negated. The patient fully recovered after empiric administration of antibiotics and glucocorticoids (initially 500 mg methylprednisolone daily over 3 days with consecutive tapering).

8.
Stem Cell Res ; 48: 101988, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32950024

RESUMO

Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by defects in motile cilia and is known to occur in about 1 in 20,000 live births (Horani and Ferkol, 2018). Among the many genes associated with PCD, NME5, a gene encoding a protein involved in ciliary function, was recently reported to be involved in PCD (Anderegg et al., 2019; Cho et al., 2020). We have established two human induced pluripotent stem cell clones from a PCD patient carrying a deletion in the NME5 gene (c.415delA (p.Ile139Tyrfs*8)).

9.
Artigo em Inglês | MEDLINE | ID: mdl-32980583

RESUMO

BACKGROUND: Biological treatments directed against IgE and IL-5 have largely improved outcomes for patients with severe type 2-high asthma. However, a fraction of patients with severe asthma show insufficient treatment outcome under anti-IgE and anti-IL-5/IL-5 receptor α antibodies. OBJECTIVE: To evaluate whether switching to dupilumab was of benefit in patients with insufficient outcome under previous anti-IgE or anti-IL-5/IL-5 receptor α therapy. METHODS: We retrospectively analyzed 38 patients who were switched to dupilumab from a previous anti-IgE or anti-IL-5/IL-5 receptor α medication because of insufficient outcome. We defined response criteria after 3 to 6 months as an improvement in at least 1 of the following criteria without deterioration in the other criteria, comparing values under dupilumab with values under previous antibody therapy: (1) increase of 3 or more in Asthma Control Test score, (2) 50% or more reduction in oral corticosteroid dose, and (3) FEV1 improvement greater than or equal to 150 mL, and classified patients as responders and nonresponders. RESULTS: Switch to dupilumab led to a response in 76% of patients. In the total cohort, Asthma Control Test score increased by a mean of 2.9 (P < .0001), whereas exacerbations decreased significantly (P < .0001) and number of oral corticosteroid-dependent patients decreased from 15 to 12. Mean FEV1 improved by 305 mL (P < .0001). Median fractional exhaled nitric oxide decreased by -30 ppb (P < .0001), whereas eosinophil counts increased by 0.17 G/L (P < .01). There were no significant differences in clinical characteristics between responders and nonresponders to dupilumab. However, patients with increased fractional exhaled nitric oxide (≥25 ppb) during previous antibody therapy were more often responders than patients with low fractional exhaled nitric oxide (<25 ppb) (P < .05). CONCLUSIONS: Altogether, we show that a switch to dupilumab in patients with insufficient outcome under previous biological therapy was effective in most patients.

10.
Respir Med ; 172: 106117, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32891937

RESUMO

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32902760

RESUMO

Novel rapid diagnostic tests (RDTs) offer huge potential to optimise clinical care and improve patient outcomes. In this study, we aim to assess the current patterns of use around the world, identify issues for successful implementation and suggest best practice advice on how to introduce new tests. An electronic survey was devised by the International Society of Antimicrobial Chemotherapy (ISAC) Rapid Diagnostics and Biomarkers working group focussing on the availability, structure and impact of RDTs around the world. It was circulated to ISAC members in December 2019. Results were collated according to the UN human development index (HDI). 81 responses were gathered from 31 different countries. 84% of institutions reported the availability of any test 24/7. In more developed countries, this was more for respiratory viruses, whereas in high and medium/low developed countries, it was for HIV and viral hepatitis. Only 37% of those carrying out rapid tests measured the impact. There is no 'one-size fits all' solution to RDTs: the requirements must be tailored to the healthcare setting in which they are deployed and there are many factors that should be considered prior to this.

12.
Orphanet J Rare Dis ; 15(1): 255, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962746

RESUMO

Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease with limited therapeutic options. We retrospectively analyzed the effects of a comprehensive 4-week inpatient pulmonary rehabilitation (PR) program in 58 patients with advanced LAM (FEV1: 45 ± 34%predicted, 6-min walk distance (6MWD): 338 ± 167 m). Exercise performance (6MWD: + 49 ± 50 m; p < 0.001) and quality of life (SF-36 physical component: + 2.4 ± 7.8 points; p = 0.049 and mental component: + 5.2 ± 12.1 points; p < 0.001) increased significantly after PR comparable to an COPD cohort. There were no clinical parameters that predicted changes in outcomes following PR. PR seems to be an effective therapeutic option even in patients with advanced LAM. TRIAL REGISTRATION: Clinical-Trials registration number: NCT04184193 ; date of registration: December 3, 2019.

15.
Lancet Respir Med ; 8(9): 853-862, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32735842

RESUMO

Background Nationwide, unbiased, and unselected data of hospitalised patients with COVID-19 are scarce. Our aim was to provide a detailed account of case characteristics, resource use, and outcomes of hospitalised patients with COVID-19 in Germany, where the health-care system has not been overwhelmed by the pandemic. METHODS: In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. To account for comorbidities, we used the Charlson comorbidity index. FINDINGS: Of 10 021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18-59 years, 382 [22%] were aged 60-69 years, 535 [31%] were aged 70-79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57-82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199). The most common comorbidities were hypertension (5575 [56%] of 10 021), diabetes (2791 [28%]), cardiac arrhythmia (2699 [27%]), renal failure (2287 [23%]), heart failure (1963 [20%]), and chronic pulmonary disease (1358 [14%]). Dialysis was required in 599 (6%) of all patients and in 469 (27%) of 1727 ventilated patients. The Charlson comorbidity index was 0 for 3237 (39%) of 8294 patients without ventilation, but only 374 (22%) of 1727 ventilated patients. The mean duration of ventilation was 13·5 days (SD 12·1). In-hospital mortality was 22% overall (2229 of 10 021), with wide variation between patients without ventilation (1323 [16%] of 8294) and with ventilation (906 [53%] of 1727; 65 [45%] of 145 for non-invasive ventilation only, 70 [50%] of 141 for non-invasive ventilation failure, and 696 [53%] of 1318 for invasive mechanical ventilation). In-hospital mortality in ventilated patients requiring dialysis was 73% (342 of 469). In-hospital mortality for patients with ventilation by age ranged from 28% (117 of 422) in patients aged 18-59 years to 72% (280 of 388) in patients aged 80 years or older. INTERPRETATION: In the German health-care system, in which hospital capacities have not been overwhelmed by the COVID-19 pandemic, mortality has been high for patients receiving mechanical ventilation, particularly for patients aged 80 years or older and those requiring dialysis, and has been considerably lower for patients younger than 60 years. FUNDING: None.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Recursos em Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Alemanha/epidemiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Respiração Artificial/estatística & dados numéricos , Adulto Jovem
17.
Eur Respir J ; 56(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32817259

RESUMO

INTRODUCTION: Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world. METHODS: REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported. RESULTS: Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p<0.001), as were those requiring hospitalisation and/or emergency department visit (from 1.14 to 0.27 per person per year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 (pre-treatment) to 5.0 mg·day-1 by week 21-24 of follow-up, sustained until week 53-56. No new safety signals were reported. CONCLUSION: These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.

18.
Chest ; 158(5): 1912-1918, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858009

RESUMO

In 2019, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) issued a substantial revision of the 2007 guideline on community-acquired pneumonia (CAP). Despite the fact that generalization of infectious disease guidelines is limited because of substantial geographic differences in microbiologic etiology and antimicrobial resistance, the ATS/IDSA guideline is frequently applied outside the United States. Therefore, this project aimed to give a perspective on the ATS/IDSA CAP recommendations related to the management of CAP outside the United States. For this, an expert panel composed of 14 international key opinion leaders in the field of CAP from 10 countries across five continents, who were not involved in producing the 2019 guideline, was asked to subjectively name the five most useful changes, the recommendation viewed most critically, and the recommendation that cannot be applied to their respective region. There was no formal consensus process, and the article reflects different opinions. Recommendations welcomed by most of the international pneumonia experts included the abandonment of the concept of "health-care-associated pneumonia," the more restrictive indication for empiric macrolide treatment in outpatients, the increased emphasis on microbiologic diagnostics, and addressing the use of corticosteroids. Main criticisms included the somewhat arbitrary choice of a 25% resistance threshold for outpatient macrolide monotherapy. Experts from areas with elevated mycobacterial prevalence particularly opposed the recommendation of fluoroquinolones, even as an alternative.

19.
Chest ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32822674

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease for which two antifibrotic drugs recently were approved. However, an unmet need exists to predict responses to antifibrotic treatment, such as pirfenidone. Recent data suggest that upregulated expression of CXCR4 is indicative of outcomes in IPF. RESEARCH QUESTION: Can quantitative, molecular imaging of pulmonary CXCR4 expression as a biomarker for disease activity predict response to the targeted treatment pirfenidone and prognosis in patients with IPF? STUDY DESIGN AND METHODS: CXCR4 expression was analyzed by immunohistochemistry examination of lung tissues and reverse-transcriptase polymerase chain reaction analysis of BAL. PET-CT scanning with the specific CXCR4 ligand 68Ga-pentixafor was performed in 28 IPF patients and compared with baseline clinical characteristics. In 16 patients, a follow-up scan was obtained 6 to 12 weeks after initiation of treatment with pirfenidone. Patients were followed up in our outpatient clinic for ≥ 12 months. RESULTS: Immunohistochemistry analysis showed high CXCR4 staining of epithelial cells and macrophages in areas with vast fibrotic remodeling. Targeted PET scanning revealed CXCR4 upregulation in fibrotic areas of the lungs, particularly in zones with subpleural honeycombing. Baseline CXCR4 signal demonstrated a significant correlation with Gender Age Physiology stage (r = 0.44; P = .02) and with high-resolution CT scan score (r = 0.38; P = .04). Early changes in CXCR4 signal after initiation of pirfenidone treatment correlated with the long-term course of FVC after 12 months (r = -0.75; P = .0008). Moreover, patients with a high pulmonary CXCR4 signal on follow-up PET scan after 6 weeks into treatment demonstrated a statistically significant worse outcome at 12 months (P = .002). In multiple regression analysis, pulmonary CXCR4 signal on follow-up PET scan emerged as the only independent predictor of long-term outcome (P = .0226). INTERPRETATION: CXCR4-targeted PET imaging identified disease activity and predicted outcome of IPF patients treated with pirfenidone. It may serve as a future biomarker for personalized guidance of antifibrotic treatment.

20.
EBioMedicine ; 57: 102885, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32650275

RESUMO

BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and γδ T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14-76,103-184CORONA-11/20 and German Research Foundation, Excellence Strategy - EXC2155"RESIST"-Project ID39087428, and DFG-SFB900/3-Project ID158989968, grants SFB900-B3, SFB900-B8.


Assuntos
Betacoronavirus/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Ativação Linfocitária/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Feminino , Humanos , Memória Imunológica/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA