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Volume 5, Emitir 3 (2015)

Artigo de Pesquisa

Asthma Metabolomics: The Missing Step for Translating Bench Work into the Clinic

Amber Dahlin, Michael J. McGeachie and Jessica A. Lasky-Su

Metabolite profiling, the systematic analysis of all metabolites, has been used successfully to identify new biomarkers for several complex diseases. In this review we describe how metabolomics data are generated, review the existing literature using metabolomics with asthma and related phenotypes, and discuss the need for more comprehensive asthma metabolomics research.

Artigo de Pesquisa

Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) as Non-Invasive Biomarkers of Remodelling in Asthma

Neveen Abd El-Moneum Hassan, Aliaё Abd-Rabou Mohamed-Hussein, Ebtssam F. Mohammed, Omnia Abd El-Moneum Mohamed, Hanan O Mohamed and Manal Mohamed Tammam Mahmoud

Rationale: Airway remodelling is clinically defined as persistent airflow obstruction despite aggressive antiinflammatory therapies. Assessment of airway remodelling by analysis of serum markers has been developed as minimally invasive procedures.

Aim of the work: Evaluate the usefulness of estimation of serum MMP-9, TIMP-1 and their ratio, as non-invasive markers of airway remodelling in asthmatics.

Patients and methods: The study included 68 asthmatics and 20 controls. Patients were classified according to levels of asthma control, severity and disease duration. Serum samples were taken to estimate levels of MMP-9, TIMP-1 and their ratio.

Results: Serum MMP-9, TIMP-1, and MMP-9/TIMP-1 were significantly higher in asthmatics than controls, in uncontrolled vs. controlled asthma (P<0.001). Also they were significantly higher in severe and moderate asthma than in mild asthma (P<0.000), and in patients with disease duration >5 years vs. <5 years (P?0.001). There was significant positive correlation between studied parameters (p<0.000) and significant negative correlation between the biomarkers and FEV1 (p<0.001).

Conclusion: Serum MMP-9, TIMP-1, and MMP-9/TIMP-1 could be considered as non-invasive markers of airway remodelling that can bypass biopsy sampling. Serum sample is easily handled and not subjected to technical error as sputum or BAL fluid.

Artigo de Pesquisa

Analysis of Short and Long Term Variability of Nasal Mucus versus Breath Condensate Inflammation Markers in Healthy Individuals

Janssens Heleen, De Prins Sofie, Schoeters Greet and Koppen Gudrun

Objective: Inflammation markers were measured in nasal mucus and exhaled breath condensate (EBC) to assess the normal variability of these markers among healthy individuals. The measurement of protein markers in those matrices is valuable to provide information on inflammation endotypes and local reaction of the immune system.

Methods: Inflammation markers (IFN-γ, IL-1β, IL-8, IL-10, IL-13 and TNF-α) in nasal mucus and EBC from six healthy adults were measured by Meso Scale Discovery technology. Nasal mucus was collected with sponges of polyurethane foam, which is a recently developed sampling technique. EBC was sampled via an optimized breath manoeuver with the RTUBETM device. Both collections were done within a limited sampling time of two minutes. The samples were taken on the same day and within a time period of twenty days for the determination of short and long term variability, respectively.

Results: All inflammation markers were detectable in nasal mucus. This was in contrast with the measurements in EBC, in which only IFN-γ, IL-8 and IL-13 were detectable in the majority of the samples. EBC collected with the applied breathing technique gave a repeatable almost constant volume (448 μL (95% CI: 429 to 467 μL)). The collected volume of nasal mucus was more variable (from 0 to 200 μL). The variability of nasal analytes was similar over the short and long time period. The nasal inflammation marker levels were more stable within an individual than between different individuals (0.72 ≤ ICC ≤ 0.96). This was in contrast with the measurements in EBC that were highly variable over time (0.08 ≤ ICC ≤ 0.51).

Conclusion: We indicate – given the good detectability and low variability of the inflammation markers determined in nasal mucus – that nasal mucus, more than EBC, is potentially a good matrix to assess inflammation in the respiratory system.

Artigo de Pesquisa

Pulmonary Embolism in Patients Hospitalized for Exacerbated COPD and Wheezing

Claire Poulet, Marine Woimant, Estelle Hoguet, Éline Magois, Marianne Auquier, Marie-Antoinette Sevestre-Pietri, Damien Basille, Claire Andréjak and Vincent Jounieaux

Background: Prevalence of pulmonary embolism (PE), a potentially lethal disease which can mimic exacerbation of chronic obstructive pulmonary disease (COPD) remains controversial.

Objective of the study: The main objective was to determine prevalence of PE in COPD patients hospitalized for exacerbation with wheezing at presentation. The secondary objectives were to compare the prevalence of PE according to COPD GOLD stages and to identify predictive factors for PE in COPD population.

Methods: We conducted a prospective study in all consecutive patients hospitalized for COPD exacerbation of unknown origin with wheezing at presentation. Patients underwent a spiral computed tomography (CT) angiography and venous lower-limb Doppler ultrasonography.

Results: 87 patients (71 males, mean age: 67.1 ± 11.2 years, 32 GOLD stage-III and 24 GOLD stage-IV patients) had an interpretable spiral CT angiography which showed eight right and five bilateral unsuspected PEs. Deep vein thrombosis was found in nine patients (associated with PE in three). The prevalence of PE and venous thromboembolism (VTE) occurred respectively in 14.9% and 21.8%. No statistical differences were found between risk factors, Geneva score or clinical signs in patients with and without PE. PE was not related to the severity of COPD.

Conclusion: There was a 14.9% prevalence of unexpected PE in patients with exacerbated COPD and wheezing at presentation. VTE events were not correlated with the severity of COPD.

Artigo de Pesquisa

Clinical Characteristics and Predictors of Mortality in Patients with Combined Pulmonary Fibrosis and Emphysema Syndrome and Lung Cancer

Yoshiaki Kitaguchi, Keisaku Fujimoto, Junichi Hotta, Shiro Horie, Jiro Hirayama and Masayuki Hanaoka

Rationale: We performed this retrospective study to clarify the clinical characteristics, survival and mortality predictors in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer.

Methods: We retrospectively reviewed the medical records of a total of 123 patients with lung cancer, as confirmed according to histological or cytological examinations. Based on the findings of chest CT, the patients were categorized into four groups: LC+normal (n=70); LC+emphysema (n=26); LC+fibrosis (n=10); LC+CPFE (n=17). The clinical characteristics and survival of the LC+CPFE group were compared with those of the other groups. In addition, mortality predictors were evaluated in the LC+CPFE group.

Results: The proportion of females was significantly higher in the LC+normal group than in the LC+CPFE and LC+emphysema groups. Significantly more patients were diagnosed with squamous cell carcinoma in the LC+CPFE group than in the LC+normal group. The proportion of patients whose primary mass was located in “nonsubpleural” areas was significantly higher in patients with CPFE who also had lung cancer in the upper lobe than in those with CPFE who also had lung cancer in the other sites. There were significant differences in survival between the LC+normal group and the other groups, whereas there were no significant differences in survival among the LC+emphysema, LC+fibrosis and LC+CPFE groups. In the LC+CPFE group, the patients with a high level of serum KL-6 at diagnosis and upper lobe lung cancer demonstrated a high risk of death. A high level of serum KL-6 at diagnosis was also independently associated with a high risk of death.

Conclusions: Patients with CPFE and lung cancer may have distinct clinical characteristics. Strict follow-up is required in patients with CPFE and lung cancer whose serum KL-6 level at diagnosis is higher than the normal range and/or the primary mass of lung cancer is located in the upper lobe.

Artigo de Pesquisa

Cisplatin Administration at Outpatient Clinics is Safe Compared to the In- Patient Usual Protocol: Findings from a Comparative Study

Sébastien Couraud, Marie Coudurier, Anne-Claire Toffart, Marie Destors, Emmanuel Villar, Mélodie Carbonnaux, Gaëlle Fossard, Delphine Farneti, Pierre-Jean Souquet and Denis Moro-Sibilot

Introduction: Cisplatin is widely used in thoracic oncology. Its main limiting adverse effect is renal toxicity. A huge intravenous hydration is known to delivery administration of high-dose cisplatin at out-patient (OP) clinic using a shorter intravenous hydration protocol. However, the safety of this strategy has never been investigated yet. Here, we aimed to provide a comparative study of creatinine clearance levels changes in OP compared to the standard inpatient protocol (IP).

Method: This is a retrospective study comparing two centers: one using the IP standard protocol and the other the OP. We used a general linear model for a confounder-adjusted assessment of the mean difference in creatinine clearance between the two groups.

Results: 227 patients were included (172 in IP and 55 in OP). Pre-cisplatin basal clearance levels were comparable between the two groups. Overall, we found neither clinically relevant nor statistically significant differences in clearance levels change between the two groups regarding each cisplatin cycle. In the multivariable analysis, we found no significant difference in clearance levels among the groups. We found a higher frequency of unexpected hospitalization in IP than in OP (18% vs. 33%; p=0.034) as well as a higher cisplatin dose reduction frequency (16% vs. 39%; p=0.002).

Conclusion: We showed that safe administration of high-dose cisplatin in outpatient clinic is feasible. Emphasize should be put on selection of eligible patients and on the mandatory oral hydration.

Artigo de Pesquisa

COPD Treatment Preference Study: A Conjoint Analysis of Preferred Drug Treatments

Emel Bulcun, Mehmet Ekici and Aydanur Ekici

Objective: The goal of this study was to determine preferences and expectation of COPD patients about their drugs used.

Method: 46 patients with COPD were involved to the study. Preferences of patients relevant to the drugs they use for COPD and their expectations from this therapy were assessed under 6 categories. 16 alternative therapy forms were established for these groups by utilizing conjoint analysis. Patients sorted 16 types of therapy per order of preference.

Results: During the Conjoint analysis the major expectation of patients from the drugs they use was the choice of number of day without complaints is to be maximum (more than 20 days). 2nd major choice of patients’ for their therapy was the choice of therapy cost to be minimum. Other choices of patients relevant to the drugs they use for therapy was respectively as follows; rapid commencing of effective period of drugs they use for reliever therapy, effective period of drugs they use for reliever therapy to be long, combined using of long term effective bronchodilator and inhaler steroid rather than seperate form. In addition, the first choice of patients for inhaler for maintenance and acute symptoms was long acting-bronchodilatator.

Conclusion: The major expectation and choice of COPD patients from their drug treatment were that the number of days without complaints was to be maximum with therapy. Other choices relevant to the drug therapy was combined forms rather than seperate and long acting bronchodilatator for maintenance treatment. Taking account of patient preferences when selecting COPD treatment may help to improve compliance with treatment.

Artigo de revisão

Review of Radiologic Infectious and Non-infectious Pulmonary Complications in Human Immunodeficiency Virus Patients

Cardenas-Garcia Jose, Talwar Arunabh, Narasimhan Mangala, Malhotra Prashant and Shah Rakesh D

The incidence of Human Immunodeficiency Virus (HIV) has decreased from its peak in the 1980’s yet there are currently more people living with HIV than ever before. As a result of highly active antiretroviral therapy (HAART), the number of opportunistic infections has decreased, with a concurrent increase in the number of non-infectious complications, not initially observed in the initial HIV epidemic. The risk of developing HIV-related pulmonary complications is strongly influenced by the degree of immunosuppression, demographic characteristics, and the use of appropriate prophylaxis against HIV-associated opportunistic infections. This article reviews the radiographic and computed tomographic (CT) manifestations of common pulmonary infections and non-infectious pulmonary complications of HIV, and highlights the importance of clinical presentation, epidemiology and immunologic status.

Relato de caso

Case Report: Sponteneous Esophageal Pleural Fistula

Ashish Deshmukh, Sunil Jadhav, Shivprasad Kasat, Hafiz Deshmukh, Chintan Yadav and Saumya Ramachandran

We are reporting a rare case of spontaneous esophageal-pleural fistula in a middle aged male patient who was presented with chest pain, breathlessness on minimal exertion, dry cough, fever. Chest x ray was done which is suggestive of hydro pneumothorax, so intercostal drain was inserted which drained frank pus. His CECT Chest done which showed fistulous track between esophagus and pleural with mediastinitis. Patient was diagnosed as a case of spontaneous esophageal pleural fistula on above mentioned background. Patient was referred to cardio thoracic surgeon for further management.

Relato de caso

Primary Pulmonary Leiomyosarcoma Treated with Chemotherapy and Surgery

Ayadi-Kaddour A, Hamrouni R, Fekih L, Marghli A and El Mezni F

Primary pulmonary leiomyosarcomas are a rare malignant tumor with generally poor prognosis. They pose important problems of differential diagnosis especially with pulmonary metastatic sarcoma. They are subdivided into two categories those originating from pulmonary parenchyma and those originating from pulmonary arteries. The authors describe a case of 54-year-old woman that had her left upper lobe mass checked. The diagnosis was made based on the microscopic examination of the percutaneous trans-thoracic needle biopsy. The general examination did not show any metastatic lesions in other areas. The treatment was based on chemotherapy followed by a surgical resection. The patient did not experience recurrences or complications.

Mini revisão

The Transpulmonary Passage of Cancer Cells: Historical Review

Wilson IB Onuigbo

Macfarlane Burnet, who is far famed in oncology, recommended during his address on the morphogenesis of cancer that researchers ought to know the historical aspects of their field. In this context, in 1952, Zeidman and Buss used experimental animals to document the transpulmonary passage of cancer cells. However, they did not supply the historical background. Therefore, this paper collates the observations of the old masters in this field from 1845 to 1899.

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