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1.
Cytokine ; 123: 154768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31276936

RESUMO

Measurement of cytokines in peripheral blood and bronchoalveolar lavage fluid (BALF) is a useful method to assess human immune responses in a large range of pulmonary diseases. One of the major pre-analytical challenges of cytokine analysis is the quality and stability of cytokines in the timeframe between sample collection and the separation of supernatant from cells. To evaluate if the method of storage may affect cytokine quantification, whole blood and BALF were collected, aliquoted, and left at room temperature (RT) to be processed at different time points. In addition, sera and BALF were left either at RT or at 4 °C for 24 h after cell separation to test cytokine variations in the absence of cells. Samples were analysed by a multiple array containing ten cytokines. Most of the cytokines analysed (interleukin (IL)-4, IL-5, IL-6, IL-12p70, IL-13, IL-17A, IL-23, interferon (IFN)-γ, and tumour necrosis factor (TNF)-α) did not show significant variations in whole blood and BALF. Levels of IL-8 however, increased after storage of whole blood and BALF for 24 h at RT. Ex vivo IL-8 production seems to correlate with higher numbers of macrophages in collected BALF. These data demonstrate that many cytokines are stable for a brief time after sample collection. For IL-8, freshly collected whole blood and BALF should be quickly processed and frozen to avoid false positive results.

3.
Sleep Breath ; 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30937718

RESUMO

STUDY OBJECTIVES: Patients with Fabry disease (FD) report impaired quality of life and excessive daytime sleepiness. Obstructive sleep apnea (OSA) is frequently reported among patients with FD; however, its prevalence and its influence on quality of life and daytime sleepiness in this population are unclear. METHODS: Patients with FD in a cohort from the University Hospital Zurich (n = 52) were one-to-two matched to healthy adult controls (n = 104) according to age, sex, and body mass index. Participants underwent structured interviews (including Short Form-36) and level-3 respiratory polygraphy. An apnea-hypopnea index of ≥ 5/h was defined as OSA and the severity of FD was quantified with the Mainz Severity Score Index (MSSI). Conditional logistic regression was used to compare the outcomes. RESULTS: In patients with FD the mean MSSI was 13.3 ± 10.5 points and OSA prevalence was 19.2% vs. 9.0% in the matched control group (p = 0.09). The apnea-hypopnea index was significantly higher in patients with FD than in the control group (0.5/h [0.2-3.0] vs. 0.2/h [0.1-1.8], p = 0.026). OSA severity was associated with impaired quality of life in four dimensions for the whole study population. Furthermore, patients with FD did report significantly higher daytime sleepiness (Epworth Sleepiness Scale 7.6 points vs. 6.3 points; p = 0.01) than healthy controls. CONCLUSION: Patients with mild FD do not have a higher OSA prevalence than matched control subjects. Differences in OSA severity did not reach clinical significance. Further studies are warranted to determine the impact of OSA in patients with moderate-to-severe FD.

4.
Clin Lung Cancer ; 20(3): e265-e273, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30914312

RESUMO

BACKGROUND: The use of 22- or 21-gauge (G) endobronchial ultrasound (EBUS) needles are recommended for lung cancer diagnosis and staging. Performance of detailed molecular workup and programmed death ligand 1 (PD-L1) staining in lung cancer patients increases the demand for tissue. The aim of this prospective, randomized two-center trial was to compare 19-G and 22-G EBUS needles regarding tissue quality, diagnostic yield, feasibility, safety, performance, and blood content. PATIENTS AND METHODS: Patients with a computed tomography scan indicative of lung cancer with mediastinal or hilar lymph node metastases were prospectively enrolled and randomized for the use of either a 19-G or a 22-G EBUS needle. A blood content score from 0 to 2 was applied. Samples were weighed, tumor cells were counted per slide, and complications and final diagnoses were documented. RESULTS: We enrolled 107 patients (53 [49.5%] in the 19-G group/54 [50.5%] in the 22-G group) and samples were weighed immediately after performing EBUS. Samples obtained with a 19-G needle contained significantly more tissue (P = .0119). Non-small-cell lung cancer-infiltrated EBUS samples contained significantly more tumor cells when sampled with a 19-G needle (P = .0312). The diagnostic yield was equally adequate in both groups. Four moderate EBUS-related bleedings occurred (2 per group), hemostasis was rapidly achieved in all cases. Further complications did not occur. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspirations with a 19-G needle contain significantly more tissue and tumor cells per slide with a safety profile similar to 22-G needles. Further research is needed to investigate the relevance of this finding in terms of molecular analyses and PD-L1 staining.

5.
J Thorac Dis ; 10(Suppl 23): S2696-S2697, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210820
6.
J Thorac Dis ; 10(Suppl 23): S2711-S2718, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210823

RESUMO

Background: Endobronchial coils have been demonstrated in three randomized, controlled trials to improve quality of life, exercise tolerance, and lung function in patients with severe emphysema. This therapy is CE-marked and commercially available in Switzerland. Coil treated patients are followed in a post-market Swiss registry to collect safety and effectiveness data in routine clinical practice. Methods: The Swiss coil registry was initiated in October 2013. At the end of November 2016, an interim analysis of all 64 patients treated in five centers was performed to evaluate safety and effectiveness at six months post treatment. Results: patients had completed bilateral treatment with 6-month follow up at the time of data analysis. Patients had very severe, symptomatic emphysema and hyperinflation [38% male, mean age 66 years, BMI 24, FEV1 30% pred., residual volume (RV) 247% pred., 6-minute walking distance (6-MWD) 272 m, St. George Respiratory Questionnaire (SGRQ) 57 points]. Up to 6 months following treatment, seven serious adverse events (SAE) were reported in 6/29 patients. No device removals were necessary. At 6 months, responder rates [% achieving the minimal clinically important difference (MCID)] were as follows: RV (-0.35 L) 76%; FEV1 (+10%) 57%; SGRQ (-4 points) 87%; 6MWD (+26 m) 60%. Conclusions: Endobronchial coil therapy performed in expert centers in Switzerland yields high 6-month responder rates across all relevant outcome.

7.
J Thorac Dis ; 10(Suppl 23): S2811-S2815, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210835

RESUMO

Bronchoscopic lung volume reduction (BLVR) has been demonstrated an efficient and safe alternative to surgery in multiple randomized trials and retrospective cohort studies. However, despite its minimal invasiveness BLVR is not without potential harm. Complications and their incidents differ significantly between the individual BLVR techniques (valves, coils, vapour or sealant) which are bearing varying device- and intervention-dependent risks. Interventional pulmonologists must be aware of potential side effects and their management to anticipate and ensure highest quality treatment of the severely ill emphysema patient.

8.
J Thorac Dis ; 10(Suppl 23): S2830-S2834, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210838

RESUMO

Surgical and bronchoscopic lung volume reduction (LVR) have been demonstrated to improve lung function, dyspnea and quality of life in patients with severe pulmonary emphysema. The most important functional prerequisite for a successful LVR is hyperinflation measured by body plethysmography. A residual volume (RV) of more than 180% predicted and a RV/total lung capacity (TLC) ratio of more than 0.58 were inclusion criteria in major LVR trials. Here we report a successful LVR in a 68-year-old man with advanced, heterogeneous emphysema without plethysmographic evidence of severe hyperinflation (RV/TLC 0.45). Computed tomography (CT) revealed severe, partly bullous upper lobe emphysema and subtle fibrotic changes with volume loss of lower lobes. Since lower lobes appeared compressed by upper lobe emphysema, these target areas were removed by thoracoscopic LVR. Four months later, the patient reported major improvements of dyspnea, FEV1 (by 1.27 L) and 6-minute walking distance (by 150 meters). LVR reduced total lung volume measured by CT-volumetry by 0.5 L and upper lobe volume by 1.85 L while lower lobe volume increased by +1.34 L. Low density volume (-950 HU) reflecting emphysema was reduced by 1.73 L. We conclude that the opposing effects of emphysema and fibrosis resulted in a barely increase in total lung volume that was only slightly reduced by LVR. Nevertheless, resection of emphysematous target areas identified by quantitative CT analysis provided major clinical and physiologic improvements related to decompression of low-compliance lower lobe areas retracted by early fibrosis. Therefore, in the combined presence of severe, heterogeneously distributed emphysema and fibrosis, LVR may improve respiratory mechanics even if RV/TLC, an established body-plethysmographic predictor of LVR success is not severely elevated.

9.
BMJ Case Rep ; 20182018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30131411

RESUMO

We discuss the case of a 44-year-old man with a refractory left lower lobe pneumonia progressing to a pulmonary abscess caused by a colobronchial fistula, a rare complication of underlying Crohn's disease. The patient presented with weight loss and signs of a pulmonary consolidation, which responded incompletely to the targeted antibiotic treatment. The causative colobronchial fistula was demonstrated by CT-guided puncture and retrograde injection of contrast medium. After fistula excision, the patient recovered rapidly with a weight gain of 4 kg within a few weeks.


Assuntos
Fístula Brônquica/complicações , Doenças do Colo/complicações , Doença de Crohn/complicações , Fístula Intestinal/complicações , Abscesso Pulmonar/etiologia , Pneumonia/etiologia , Adulto , Humanos , Masculino
10.
J Thorac Dis ; 10(5): 2722-2730, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29997934

RESUMO

Background: Lung volume reduction surgery (LVRS) is a treatment option for selected patients with severe chronic obstructive pulmonary disease (COPD) and emphysema. The positive effects of LVRS on exercise capacity are well known. In contrast, the effect of LVRS on daily physical activity (PA) is less clear. Methods: In a prospective case-control study we evaluated selected patients with severe COPD and emphysema who underwent LVRS and COPD patients following usual care. Controls were matched for age, severity of airflow obstruction (FEV1) and hyperinflation [residual volume to total lung capacity (RV/TLC)]. Treatment effect of LVRS on activity parameters was analysed using univariable regression model adjusting for treatment group. Results: A total of 19 patients underwent LVRS and 16 COPD patients without a surgical intervention during the study period were included. The median (quartile) FEV1%pred was 28% (range, 21-33%), RV/TLC was 69% (range, 64-73%) in cases while controls had a median (quartile) FEV1%pred of 33% (range, 28.5-49.5%) and a RV/TLC of 58% (range, 49-61%). Age and body mass index (BMI) were comparable between both groups. Number of steps per day following LVRS was comparable to before the intervention (mean change: -115, 95% CI: -994.6 to 764.3, P=0.779) and was not significantly different to the change in control subjects (mean treatment effect: 931.4, 95% CI: -252.4 to 2,115.1, P=0.117). Conclusions: The results from this study reveal that patients undergoing LVRS did not increase their daily level of PA despite improvement of exercise capacity and symptoms.

11.
BMJ Open Respir Res ; 5(1): e000277, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29713479

RESUMO

Introduction: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Methods: Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Results: Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6-61) years in men, 34 (13-67) in women) were included. The greatest decrease of FEV1/FVC z-scores was observed in Classic men (-0.048 per year, 95% CI -0.081 to -0.014), compared with the Later-Onset men (+0.013,95% CI -0.055 to 0.082), Classic women (-0.008, 95% CI -0.035 to +0.020) and Later-Onset women (-0.013, 95% CI -0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV1 decline. FEV1/FVC z-score decrease was significantly reduced after initiation of ERT initiation (-0.045 compared with -0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Conclusion: Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.

12.
Curr Med Res Opin ; 34(11): 1927-1932, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29625529

RESUMO

OBJECTIVE: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses. METHODS: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying). RESULTS: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p < .001) on utility (+0.101 and +0.061, respectively). When combined with selected baseline characteristics and time, Coils and Standard of Care (SoC) generated more QALYs than SoC alone in all scenarios, with incremental lifetime benefit ranging from 0.29-0.55 QALYs. CONCLUSIONS: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.


Assuntos
Broncoscopia/métodos , Enfisema , Assistência Centrada no Paciente/métodos , Qualidade de Vida , Adulto , Manuseio das Vias Aéreas/métodos , Manuseio das Vias Aéreas/psicologia , Análise Custo-Benefício , Progressão da Doença , Enfisema/economia , Enfisema/psicologia , Enfisema/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
14.
Eur J Cardiothorac Surg ; 54(3): 565-571, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538689

RESUMO

OBJECTIVES: Pulmonary hypertension (PH) is considered a contraindication for lung volume reduction surgery (LVRS). Because, it has been reported that endobronchial lung volume reduction may have a beneficial effect without increased mortality in patients with emphysema and PH, we evaluated its effect on PH in patients undergoing LVRS. METHODS: From January 2014 until June 2016, 119 LVRSs were performed at Zurich University Hospital. PH was a contraindication for patients with homogeneous emphysema but was acceptable for those with heterogeneous emphysema. Thirty patients underwent echocardiography before and after LVRS, 10 of whom had preoperative systolic pulmonary artery pressures >35 mmHg and 20 of whom had normal systolic pulmonary artery pressure. The effect of LVRS on pulmonary artery pressure, lung function and survival was analysed. RESULTS: Ninety-day mortality for all 30 patients was 0, and the postoperative course did not differ significantly between the 2 groups. In patients with PH, the median systolic pulmonary artery pressure decreased from 41 mmHg [interquartile range (IQR) 39-47] to 37 mmHg (IQR 36-38, P = 0.04). These patients had an improvement of forced expiratory volume in 1 s from the median 27% predicted (IQR 23-34) to 33% (IQR 28-40, P = 0.007) 3 months postoperatively. CONCLUSIONS: If further confirmed in other cohorts, mild to moderate PH may no longer be considered a contraindication for LVRS in patients with heterogeneous emphysema.


Assuntos
Hipertensão Pulmonar , Pulmão , Pneumonectomia , Enfisema Pulmonar , Adulto , Idoso , Ecocardiografia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/cirurgia , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/mortalidade , Pneumonectomia/estatística & dados numéricos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/mortalidade , Enfisema Pulmonar/cirurgia
16.
Melanoma Res ; 28(3): 230-236, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29485531

RESUMO

The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today's standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB-IV melanoma treated with BRAF/MEK inhibitors and immune checkpoint inhibitors. A description of the sarcoidosis-related manifestations was provided from patients' records. We observated eight cases of SLRs in a cohort of 200 patients. The clinical courses were characterized by a variety of symptoms, accompanied by cutaneous signs and extracutaneous manifestations such as bilateral, hilar lymphadenopathy. We identified a histologically granulomatous inflammation involving the skin, the lungs, and the lymph nodes. Two patients presented with cutaneous lesions only, and three patients had lung involvement only. Three patients achieved complete and partial response of the melanoma disease, and three patients had stable disease. Disease progression was documented in two patients. The reported immune-related adverse events were mild to severe and in most of the cases were continued without any treatment cessation. SLRs appear during treatment with both kinase and immune checkpoint inhibitors. Awareness of these can avoid misdiagnosis of disease progression and unnecessary treatment changes.


Assuntos
Imunoterapia/métodos , Melanoma/tratamento farmacológico , Sarcoidose/etiologia , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sarcoidose/induzido quimicamente , Sarcoidose/patologia , Neoplasias Cutâneas/patologia , Adulto Jovem
17.
Ann Thorac Surg ; 105(2): 379-385, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29223424

RESUMO

BACKGROUND: Lung volume reduction surgery (LVRS) has been proven to be a successful procedure and can be performed with low mortality when defined selection criteria are met. We hypothesized good outcome and low mortality after LVRS for selected patients with severe hyperinflation and nonhomogeneous morphology even when diffusion capacity of the lung for carbon monoxide (Dlco) is less than 20%. METHODS: The study included all patients scheduled for LVRS between March 2005 and May 2014 with a preoperative Dlco of less than 20%. Postoperative 90-day mortality was the primary end point. Secondary end points were postoperative lung function and surgical morbidity at 3, 6, and 12 months. RESULTS: Included were 33 patients with a median forced expiratory volume in 1 second of 23% (interquartile range, 19% to 28%), a median diffusion capacity of 15% (interquartile range, 13% to 18%), and a median hyperinflation of 76% (residual volume-to-total lung capacity ratio of 70% to 76%). Mean follow-up was 44.8 months (range, 10 to 141 months). Heterogeneous emphysema was present in 26 patients, and 7 showed intermediately heterogeneous morphology. Sixteen procedures were bilateral, and 31 were performed by video-assisted thoracoscopic surgery. The 90-day mortality was 0%. Median forced expiratory volume in 1 second percentage predicted at 3 months increased from 23% to 29% (p < 0.001). Median Dlco increased from 15% to 24% (p < 0.001), and median hyperinflation decreased from 76% to 63% (p < 0.001). A prolonged air leak exceeding 7 days occurred in 16 patients (48.5%), and 6 required reoperation for fistula closure. The 7 patients with intermediately heterogeneous emphysema showed a median increase in forced expiratory volume in 1 second from 20% preoperatively to 28% postoperatively (p = 0.028). CONCLUSIONS: Selected patients with severely impaired Dlco of less than 20% can cautiously be considered as potential candidates if hyperinflation is severe and the lungs show areas with advanced destruction as targets for resection.


Assuntos
Pulmão/cirurgia , Pneumonectomia/métodos , Capacidade de Difusão Pulmonar/fisiologia , Enfisema Pulmonar/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Reoperação , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Cancer Immunol Immunother ; 67(1): 127-134, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28983773

RESUMO

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (-4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Ipilimumab/efeitos adversos , Pulmão/efeitos dos fármacos , Melanoma/tratamento farmacológico , Idoso , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Respiratória
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