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BACKGROUND: In amyotrophic lateral sclerosis (ALS) prognosis is poor due to progressive weakening of the respiratory muscles. Survival and quality of life can be improved by noninvasive ventilation (NIV), which is initially applied while sleeping. The indication for NIV is based on pulmonary function testing (PFT) and polysomnography (PSG) with capnography (tCO2). While it is desirable to predict nocturnal ventilation by waking PFT in ALS, the parameters suited for reliable predictions remain elusive. METHODS: We retrospectively analyzed parameters derived from PFT (spirometry, body plethysmography, diffusion capacity, respiratory muscle testing) and blood gas analysis, PSG and tCO2 in 42 patients with ALS (27 men, 15 women, age 69 ± 12.1 years) and performed Spearman's correlation analysis of daytime waking parameters and nighttime sleep parameters. RESULTS: 28 patients (66.7%) showed restrictive impairment of ventilation and 15 patients (48.3%) showed insufficiency of the respiratory musculature. There was no obstructive impairment of ventilation. We did not observe any significant correlations between any single daytime PFT parameter with nocturnal pCO2. However, there were significant correlations between the ratios PIF/PEF, MEF50/MIF50, DLCO/VA as well as FEV1/FVC and nocturnal pCO2. Highly normal FEV1/FVC and Krogh-Factor (DLCOc/VA) indicated nocturnal hypercapnia. Furthermore, waking hypercapnia, concentrations of bicarbonate and base excess were each positively correlated with nocturnal hypercapnia. CONCLUSIONS: Waking PFT is not a good predictor of nocturnal ventilation. Inspiratory parameters as well as the ratios FEV1/FVC and DLCO/VA performed best and should be included in the interpretation. Our analyses confirm the relevance of inspiratory muscle weakness in ALS. PSG and tCO2 remain the gold standard for the assessment of nocturnal ventilation.
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INTRODUCTION: Pirfenidone was the first anti-fibrotic drug approved in Europe in 2011 for the treatment of mild-to-moderate idiopathic pulmonary fibrosis. OBJECTIVES: To investigate the clinical course of mild-to-moderate idiopathic pulmonary fibrosis in pirfenidone-treated patients in a real-world setting. METHODS: The non-interventional study was conducted at 18 sites in Germany from 6/2014-12/2016. Adult patients with mild-to-moderate idiopathic pulmonary fibrosis were treated with pirfenidone (escalated from 3×1 to 3×3 capsules of 267 mg/day within 3 weeks) for 12 months. The observation period comprised 4 follow-up visits at months 3, 6, 9 and 12. Disease progression was defined as decrease of ≥10% in vital capacity or ≥15% in diffusing capacity of the lung for carbon monoxide (DLCO) and/or ≥50m in 6-minute walking distance vs. baseline, or "lack of response/progression" as reason for therapy discontinuation. RESULTS: A total of 51 patients (80.4% male, mean age 70.6 years) were included in the full analysis set. Disease progression at any visit was reported for 23 (67.6%) of 34 patients with available data. Over the course of the study, lung function parameters, physical resilience, impact of cough severity on quality of life, and the mean Gender, Age and Physiology Index (stage II) remained stable. In total, 29 patients (56.9%) experienced at least one adverse drug reaction (11 patients discontinued due to adverse drug reactions); serious adverse reactions were reported in 12 patients (23.5%). CONCLUSIONS: The results of this study are in line with the established benefit-risk profile of pirfenidone. Therefore, pirfenidone can be considered a valuable treatment option to slow disease progression in mild-to-moderate idiopathic pulmonary fibrosis. NCT02622477.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fibrosis Pulmonar Idiopática , Piridonas , Adulto , Humanos , Masculino , Anciano , Femenino , Calidad de Vida , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Tos , Progresión de la EnfermedadRESUMEN
BACKGROUND: High-frequency jet ventilation (HFJV) is used in pneumological endoscopy for rigid, diagnostic, and therapeutic bronchoscopies. It is unclear to what extent the unobstructed flow of respiratory gas from the patient's lungs causes microbial contamination of the surrounding air. MATERIAL AND METHODS: After the start of the HFJV (15 min) in 16 rigid bronchoscopies, airborne pathogen measurements were taken directly at the distal endoscope outlet, at examiner height (40 cm above the endoscope outlet), at a 2 m distance from the endoscope in the room and at the supply air outlet of the examination room using an RCS air sampler. The number and type of pathogens isolated in the air samples were then determined, as well as germs in the bronchoalveolar lavage fluid (BALF) from the patient's lungs. RESULTS: An increased bacterial density (136 and 114 CFU/m3) was detected directly at the distal end of the endoscope and at examiner height at a distance of 40 cm, which decreased significantly with increasing distance from the bronchoscope (98 CFU/m3 at a distance of 2 m and 82 CFU/m3 at the supply air outlet). The most frequently detected bacteria were Staphylococcus spp., Micrococcus spp. and Bacillus spp. In the BALF, pathogens could only be cultivated in four of 16 samples, but the same pathogens were detected in the BALF and the ambient air. CONCLUSION: When performing a rigid bronchoscopy, in which patients are mechanically ventilated in a controlled manner using an open HFJV system, there is an increased pathogen load in the ambient air and therefore a potential risk for the examiner.
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Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time. The evidence was discussed by a multidisciplinary committee of experts. Then, recommendations were formulated for twelve questions on important issues of diagnosis and treatment strategies. Recently published national and international guidelines for ILDs and HP were considered. Detailed background information on HP is useful for a deeper insight into HP and the handling of the guideline.
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OBJECTIVES: Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). METHODS: Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). RESULTS: Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. CONCLUSION: When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.
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Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints. To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the "sick recovered" from the "healthy recovered." Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.
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COVID-19 , Triaje , Humanos , Síndrome Post Agudo de COVID-19 , COVID-19/complicaciones , Biomarcadores , FatigaRESUMEN
The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.
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Antiasmáticos , Asma , Femenino , Embarazo , Humanos , Óxido Nítrico , Asma/terapia , Asma/tratamiento farmacológico , Antiasmáticos/uso terapéutico , Biomarcadores , Desensibilización InmunológicaRESUMEN
PURPOSE: Transport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion. Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT). METHODS: Pigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT. RESULTS: Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae. CONCLUSION: Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR.
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Inmunoglobulina A Secretora , Receptores de Inmunoglobulina Polimérica , Mucosa Respiratoria , Animales , Antibacterianos/inmunología , Antibacterianos/farmacología , Inmunoglobulina A Secretora/inmunología , Inmunoglobulina A Secretora/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Ratones , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Receptores de Inmunoglobulina Polimérica/inmunología , Receptores de Inmunoglobulina Polimérica/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismoRESUMEN
Bronchial asthma is one of the most common chronic diseases worldwide and affects more than 300 million patients. Allergic asthma affects the majority of asthmatic children as well as approximately 50% of adult asthmatics. It is characterized by a Th2-mediated immune response against aeroallergens. Many aspects of the overall pathophysiology are known, while the underlying mechanisms and predisposing factors remain largely elusive today. Over the last decade, respiratory colonization with Staphylococcus aureus (S. aureus), a Gram-positive facultative bacterial pathogen, came into focus as a risk factor for the development of atopic respiratory diseases. More than 30% of the world's population is constantly colonized with S. aureus in their nasopharynx. This colonization is mostly asymptomatic, but in immunocompromised patients, it can lead to serious complications including pneumonia, sepsis, or even death. S. aureus is known for its ability to produce a wide range of proteins including toxins, serine-protease-like proteins, and protein A. In this review, we provide an overview of the current knowledge about the pathophysiology of allergic asthma and to what extent it can be affected by different toxins produced by S. aureus. Intensifying this knowledge might lead to new preventive strategies for atopic respiratory diseases.
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Asma , Hipersensibilidad Inmediata , Infecciones Estafilocócicas , Adulto , Niño , Humanos , Staphylococcus aureus/metabolismo , Asma/etiología , Enterotoxinas/metabolismo , AlérgenosRESUMEN
The polypeptide TFF3 belongs to the trefoil factor family (TFF) of lectins. TFF3 is typically secreted from mucous epithelia together with mucins. Both intestinal and salivary TFF3 mainly exist as disulfide-linked heterodimers with IgG Fc binding protein (FCGBP). Here, we investigated bronchial tissue specimens, bronchial secretions, and bronchoalveolar lavage (BAL) fluid from patients with a chronic obstructive pulmonary disease (COPD) background by fast protein liquid chromatography and proteomics. For the first time, we identified different molecular forms of TFF3 in the lung. The high-molecular mass form represents TFF3-FCGBP oligomers, whereas the low-molecular mass forms are homodimeric and monomeric TFF3 with possibly anti-apoptotic activities. In addition, disulfide-linked TFF3 heterodimers with an Mr of about 60k and 30k were detected in both bronchial secretions and BAL fluid. In these liquids, TFF3 is partly N-terminally truncated probably by neutrophil elastase cleavage. TFF3-FCGBP is likely involved in the mucosal innate immune defense against microbial infections. We discuss a hypothetical model how TFF3 might control FCGBP oligomerization. Furthermore, we did not find indications for interactions of TFF3-FCGBP with DMBT1gp340 or the mucin MUC5AC, glycoproteins involved in mucosal innate immunity. Surprisingly, bronchial MUC5AC appeared to be degraded when compared with gastric MUC5AC.
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Proteínas Portadoras , Mucinas , Humanos , Bronquios/metabolismo , Moléculas de Adhesión Celular/metabolismo , Disulfuros/metabolismo , Inmunoglobulina G/metabolismo , Mucinas/metabolismo , Factor Trefoil-2/metabolismo , Factor Trefoil-3/metabolismo , Fragmentos Fc de InmunoglobulinasRESUMEN
Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.
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Susceptibilidad a Enfermedades , Neuroinmunomodulación , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/metabolismo , Infecciones del Sistema Respiratorio/complicaciones , Animales , Enfermedad Crónica , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Enfermedades Respiratorias/diagnóstico , Infecciones del Sistema Respiratorio/etiologíaRESUMEN
A wide variety of drugs and substances have the potential to damage the respiratory system by different mechanisms. Clofazimine is an anti-leprosy drug that is normally only prescribed for a few years. It has a very long half-life, and crystalline deposition of the drug in various tissues has been documented. But up to now, no fatalities due to pulmonary damage have been described. We report the case of a patient who took clofazimine for almost 27 years as off-label treatment for Melkersson-Rosenthal syndrome. He suffered from progressive dyspnea, productive cough, and occasional hemoptysis. X-ray and CT of the thoracic organs revealed extensive multilocular, compact, tumor-like infiltrates with central necrosis in both lungs. Pulmonary function tests showed restrictive impairment and manifest hypoxemia. Histology of lung biopsies revealed intense interstitial accumulation of histiocytes and marked deposition of crystalline foreign material. The patient died from progressive respiratory failure. Autopsy revealed crystalline deposition and a histiocytic reaction in many other parenchymal organs. Conclusion: Pulmonary parenchymal deposition of drug crystals is a rare mechanism of drug-induced pulmonary diseases. Long-standing, off-label use of clofazimine may cause severe destruction of the lungs and can be fatal.
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Clofazimina/efectos adversos , Síndrome de Melkersson-Rosenthal , Insuficiencia Respiratoria , Biopsia , Resultado Fatal , Hemoptisis , Humanos , Masculino , Síndrome de Melkersson-Rosenthal/inducido químicamente , Síndrome de Melkersson-Rosenthal/tratamiento farmacológicoRESUMEN
BACKGROUND: Inhalation therapy is the backbone of asthma and COPD control. However, inhaler adherence and device mishandling continue to be a problem in real life. Some studies have shown that using a patient-preferred inhaler may reduce device handling errors and improve adherence to prescribed chronic inhaler drug therapy. The aim of this study was to compare the preferences for commonly used inhaler devices in Germany in patients with chronic obstructive respiratory disease. We also pursued the question which properties of an inhaler device are particularly important to the user and what effects age, gender and type of disease (asthma or COPD) may have on device preference and handling errors. METHODS: Prospective, open-label cross-sectional study in which 105 patients with asthma (58%) or COPD (42%) participated. Validated checklists were used to objectively assess inhaler technique and errors with 10 different placebo devices. For each device, patients were asked to test the handling, to assess the device properties and to name the device that they would most or least prefer. RESULTS: Across the 10 placebo inhaler devices tested, patients needed an average of 1.22 attempts to error-free use. The device with the lowest mean number of attempts was the Turbohaler® (1.02), followed by the Nexthaler® (1.04), the Diskus® (1.07) and the Spiromax® (1.10). Patients over 60 years vs. younger age (p = 0.002) and COPD vs. asthma patients (p = 0.016) required more attempts to ensure correct use. 41% of the study participants chose one of the devices they already used as the most preferred inhaler. Overall, 20% opted for the Spiromax®, 15% for the Nexthaler® and 14% for the Turbohaler® or a pMDI. The least preferred device was the Elpenhaler® (0%). From a selection of 7 predefined inhaler attributes, patients stated easy handling as the most important for them. This was followed by short inhalation time and low inhalation resistance. CONCLUSIONS: Patient preference may vary between inhaler devices. The lowest number of attempts to error-free use was reported for the Turbohaler® and the Nexthaler®. The Spiromax® and the Nexthaler® achieved the best overall ratings and were the devices most preferred by patients.
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Asma/tratamiento farmacológico , Nebulizadores y Vaporizadores , Prioridad del Paciente , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Adolescente , Adulto , Asma/psicología , Estudios Transversales , Diseño de Equipo , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/psicología , Autoadministración/instrumentación , Autoadministración/normas , Adulto JovenRESUMEN
BACKGROUND: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. METHODS: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. RESULTS: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. CONCLUSIONS: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.
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Fosfolípidos/sangre , Neumonía/sangre , Esfingomielina Fosfodiesterasa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Ceramidas/sangre , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/diagnóstico , Femenino , Humanos , Mediadores de Inflamación/sangre , Lipidómica , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Investigación Biomédica Traslacional , Adulto JovenRESUMEN
Pulmonary hypertension is a chronic, incurable disease with poor prognosis. The therapeutic aim is a stabilization of patients showing signs of right heart failure as well as disease progression. A pulmonary hypertension is diagnosed in patients displaying a mean pulmonary arterial pressure of > 25 mmHg in resting state. Invasively measured hemodynamics evaluated by right heart catheterization (mean pulmonary arterial pressure [mPAP], pulmonary arterial wedge pressure [PAWP], diastolic pressure gradient [DPG] and pulmonary vascular resistance [PVR]) allows to differentiate between pre-capillary, post-capillary and combined pulmonary hypertension, which constitutes the basis for classification. Diagnostics and therapy shall occur within a center of expertise. Currently, 10 medications belonging to 5 substance classes are approved. Combination therapy should be introduced early. In accordance with risk stratification, therapy is oriented towards estimated 1-year survival as opposed to single target values. If pulmonary hypertension is associated with left heart disease (group 2) or lung disease (group 3), optimal care of the primary disease should be paramount. These associations make up for a greater proportion of patients than idiopathic pulmonary arterial hypertension (PAH). In isolated cases, patients of group 2 may be treated in centers of expertise within the scope of medical studies. Patients with PAH may be categorized into typical versus atypical PAH. For patients with atypical PAH, an initial monotherapy is to be introduced. In case of chronic thromboembolic pulmonary hypertension, the possibility of an operative pulmonary endarterectomy should be evaluated. To date, the only approved drug is Riociguat, a stimulator of the soluble guanylate cyclase.
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Hipertensión Pulmonar , Cateterismo Cardíaco , Hemodinámica , Humanos , Hipertensión Pulmonar/clasificación , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Presión Esfenoidal Pulmonar , Resistencia VascularRESUMEN
The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica as the underlying model to comprehensively address effects on subsequent immune responses. Carriage was associated with the stimulation of Bordetella-specific CD4âº, CD8âº, and CD4âºCD25âºFoxp3⺠T cell responses, and broad transcriptional activation was observed in CD4âºCD25⺠T cells. Importantly, transfer of leukocytes from carriers to acutely B. bronchiseptica infected mice, resulted in a significantly increased bacterial burden in the recipient's upper respiratory tract. In contrast, we found that respiratory B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. Adaptive responses to vaccination and influenza A virus infection, were unaffected by B. bronchiseptica carriage. These data showed that there were significant immune modulatory processes triggered by B. bronchiseptica carriage, that differentially affect subsequent immune responses. Therefore, our results demonstrated the complexity of immune regulation induced by respiratory bacterial carriage, which can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.
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Bordetella bronchiseptica/inmunología , Coinfección/inmunología , Infecciones del Sistema Respiratorio/inmunología , Linfocitos T Reguladores/microbiología , Vacunación , Inmunidad Adaptativa/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Infecciones por Bordetella/sangre , Infecciones por Bordetella/inmunología , Infecciones por Bordetella/microbiología , Infecciones por Bordetella/prevención & control , Bordetella bronchiseptica/genética , Antígenos CD5/análisis , Portador Sano/inmunología , Portador Sano/microbiología , Coinfección/sangre , Coinfección/microbiología , Coinfección/prevención & control , Virus de la Influenza A/genética , Virus de la Influenza A/inmunología , Listeria monocytogenes/genética , Listeria monocytogenes/inmunología , Ratones , Ratones Endogámicos BALB C , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/prevención & control , Linfocitos T Reguladores/inmunologíaRESUMEN
In symptomatic malignant pleural effusions, mostly in a palliative situation, therapeutic procedures should be chosen to improve dyspnoea and the concomitant impairment of quality of life. Indwelling pleural catheters (IPC) have played an increasing role in recent years. The efficacy and safety of this method have not been adequately clarified under real-life clinical conditions. 94 patients, in whom IPC had been implanted because of a clinical indication, were analysed retrospectively with respect to efficacy and safety, together with patient characteristics, peri- and postinterventional complications, e.g. infections or pneumothorax, and long-term follow-up - with special emphasis on the occurrence of a pleurodesis. Overall, 89.5% (n = 85) of the patients received an IPC due to a recurrent pleural effusion caused by a malignant primary disease. The average duration of hospitalisation for patients did not decease as a result of their incurable condition and was 3.29 days. In 21.2% (n = 20) of the patients, pleurodesis occurred. Method-related complications arose for 33.2% (n = 32) of the patients, although further treatment was only needed in 8 patients. Late complications developed for 9 of the patients observed. The average survival period after implantation was 88.72 days. The results show that IPC is a technically straightforward, minimally invasive alternative to recurrent punctures or other methods of pleurodesis. A major benefit is the possibility of outpatient care.
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Catéteres de Permanencia/efectos adversos , Derrame Pleural Maligno/epidemiología , Derrame Pleural Maligno/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pleurodesia , Neumotórax , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.