A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.

Summary: Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.

Women's leadership in clinical research: A retrospective observational study over two decades in Spain.

BACKGROUND AND OBJECTIVE: Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. MATERIALS AND METHODS: Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. MAIN OUTCOME: proportion of CI led by female doctors (FD) during the study period. SECONDARY OUTCOMES: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. DATA SOURCES: Research Ethics Committee (REC) and Human Resources Department registries. RESULTS: During the study, the REC approved 8466 protocols, 52% (4408/8466) were EC, the rest were NIR. Women led 39.7% (3360/8466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1391/4408) and 48.5% (1969/4058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. CONCLUSIONS: Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research.

[Non-tuberculous mycobacterial infection in patients with non-cystic fibrosis bronchiectasias]. / Infección por micobacterias no tuberculosas en pacientes con bronquiectasias no causadas por fibrosis quística.

AIMS: To know the characteristics and prevalence of non-tuberculous mycobacterial infection infection in patients with non-cystic fibrosis bronchiectasis. PATIENTS AND METHODS: A retrospective descriptive study of NCFB adult patients whose disease had been followed-up for at least two years was performed. RESULTS: A total of 68 subjects were included, 50 females (73.5%), with mean age of 63.31± 16.2 years. The most frequent etiology of the non-cystic fibrosis bronchiectasis was COPD in 28 cases (41.2%) with a light-moderate pulmonary involvement and Pseudomonas aeruginosa (P. aeruginosa) colonization (70.6%). Seven patients (10.3%) had MNT infection, six of whom had Mycobacterium avium complex (7.35%). Four patients (57.14%) were treated. In the infected patients, P. aeruginosa and the use of inhaled steroids were observed with less frequency. There were no significant differences between the infected and non-infected patients in relation to spirometric values. CONCLUSIONS: The non-cystic fibrosis bronchiectasis could be considered a risk factor for non-tuberculous mycobacterial infection.

Asthma diagnosis is not associated with obesity in a population of adults from Madrid.

BACKGROUND: Several studies have suggested a relationship between asthma and obesity; however, this relationship is unclear when obesity is compared with bronchial hyperresponsiveness to methacholine. AIM: To determine whether obesity is associated with a diagnosis of asthma. METHODS: We conducted a cross-sectional study in a population of Spanish adults in the north of Madrid, Spain between 2003 and 2007. The patients included had experienced asthma symptoms during the previous year, but had a ratio of forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity (FVC) of > 70%. Diagnosis was confirmed by the presence of symptoms and demonstration of bronchial hyperresponsiveness to methacholine. Obesity was measured by body mass index (BMI). Adjusted odd ratios (OR) were obtained by logistic regression. RESULTS: Of a total of 1424 patients included, 251 (17.6%) were diagnosed with asthma. These patients were younger (P < .001) and had lower BMI (P < .001) and lung function parameters (FEV1 and FEV1/FVC ratio) than individuals without asthma (P < .001). After adjusting the model for age, gender, baseline FEV1, and FEV1/FVC ratio, patients with overweight or obesity were not more frequently diagnosed with asthma than those with normal weight (OR, 0.848 [95% confidence interval (CI), 0.59-1.20]; and OR, 0.616 [95% CI, 0.38-0.99], respectively). In addition, obese males were more frequently diagnosed with asthma than obese females (P < .041). CONCLUSIONS: In this study, obesity and overweight were not associated with a diagnosis of asthma based on the presence of consistent symptoms and demonstration of airway responsiveness to methacholine.

[Diagnostic imaging departments' responses to terrorist attempts with multiple victims.]. / Respuesta de los servicios de radiodiagnóstico ante ataques terroristas con múltiples víctimas.

OBJECTIVES: To analyze whether the radiological management of seriously injured victims from the March 11 terrorist attempt was affected by the large number of victims treated at two hospitals in Madrid. To evaluate the organization for providing imaging services, detect failings, and propose a protocol for diagnostic imaging departments. MATERIAL AND METHODS: Two hundred and fifty one patients arrived at hospital A and 36 at hospital B. Both centers have emergency imaging areas and protocols for the treatment of patients with multiple trauma. We compared organizational aspects (classification, identification), material resources, human resources, healthcare resources (number and type of examinations), as well as the initial radiological management with the usual protocol and with the recommendations for incidents with multiple victims. RESULTS: In hospital A, patients' injuries were classified as severe (175) or minor (76); in hospital B, injuries were classified as extremely severe (13), severe (4), or minor (19). Additional staff were assigned to the emergency imaging areas in both hospitals. In hospital A, 62 portable plain-film radiographs, 39 ultrasonographic examinations, 25 cranial CT examinations, 6 cervical CT examinations, 2 chest CT examinations, and 2 abdominopelvic CT examinations were performed. In hospital B, 19 portable plain-film radiographs (74 in total), 9 ultrasonographic examinations, 17 cranial-chest-abdominopelvic CT examinations, 2 cervical CT examinations, 2 orbital CT examinations, and 2 CT examinations of the sinuses were performed. CONCLUSION: In both hospitals, each victim was managed as if he or she were the only patient. The discrepancies between the two hospitals were due to differences in the usual protocol for multiple trauma patients. In light of the organizational errors discovered, we propose a plan of action based on the identification and progressive activation of material and human resources until sufficient levels are achieved.

Relationship between the upper airway and obstructive sleep apnea-hypopnea syndrome in morbidly obese women.

BACKGROUND: The authors studied changes in the upper airway in morbidly obese women and the relationship to sleep apnea-hypopnea syndrome (OSAS). METHODS: Patients underwent a cardiorespiratory polygraphic study, respiratory function test (spirometry, plethysmography, maximum inspiratory pressures and arterial blood gas analysis), and computed tomographic studies of the upper airway. RESULTS: 40 morbidly obese women being evaluated for bariatric surgery (mean age 39.6 +/- 9.6 years old, BMI 48.7 +/- 5.6 kg/m2) were studied. 37 women had OSAS, and 14 had severe OSAS. Results on respiratory function tests were normal. BMI and weight had a positive correlation with apnea-hypopnea index (AHI), apnea index (AI), desaturation index (DI), lowest oxygen saturation and CT90. Uvula diameter had a negative correlation with FEV1, FVC, VC IN and a positive correlation with TLC. Retropharynx soft tissue at the retropalatal level had a negative correlation with FEV1, FVC and VC IN. The oropharynx area at maximal inspiration (total lung capacity) obtained a negative correlation with the AHI (r = - 0.423, P = 0.044), AI (r = - 0.484, P = 0.042) and DI (r = - 0.484, P = 0.019). CONCLUSIONS: Prevalence of OSAS in morbidly obese women is very high. Our results show the significant correlation between BMI and AHI in morbidly obese women. Uvula diameter and retropharynx soft tissue are the upper airway parameters with higher relationship with pulmonary function. A reduction in the cross-sectional area of the airway at the level of the oropharynx could be related to the severity of OSAS in morbidly obese women.

How are the ancient cystic fibrosis patients? Cystic fibrosis diagnosed over 60 years-old.

BACKGROUND AND AIMS: To specify the prevalence of patients diagnosed with CF at age of ≥60 year-old and to analyze their characteristics. PATIENTS AND METHODS: Observational study of CF patients which were diagnosed at age ≥60 year-old. The analyzed variables were: age, sex, nationality, lung function parameters, conditions present at diagnosis, microbiological characteristics and genetic findings. RESULTS: eight patients were included. 7 patients were female (87.5%) with a mean age of 70.6 years (median 71.5 years, range 60-78 years). The most important findings were: sweat test >60 mEq/l; heterozygotes F508del; bronchiectasis in CT; methicillin-sensitive Staphylococcus aureus (50%) in sputum. The most patients presented a normal or mild obstructive lung function. CONCLUSIONS: CF must also be considered a disease diagnosed in adulthood, incorporating the sweat test within the usual techniques of differential diagnosis in patients with different diseases associated with CF, because genetic counselling is esencial.

Multidrug-resistant tuberculosis without HIV infection: success with individualised therapy.

OBJECTIVE: To evaluate the results of the treatment of non-HIV-infected multidrug-resistant tuberculosis (MDR-TB) patients admitted to a tuberculosis unit in a reference centre between June 1998 and December 2000. RESULTS: Twenty-five patients were studied (23 men). Empirical treatment was selected according to drugs previously used and adjusted according to in vitro test results. Patients had previously received an average of 5.5 drugs and were resistant to an average of 4.7 drugs. They were treated with a median number of four drugs (an injectable drug plus three oral drugs) for a median of 18 months. Ofloxacin and cycloserine was used in 17 cases (68%), ethionamide/prothionamide in 18 (72%) and para-aminosalicylic acid in 12 patients (48%). Psychological support and counselling was provided. Two patients required surgery. Globally, 21 patients (84%) met cure criteria. After a 24-month follow-up, none of the 21 patients who successfully completed treatment presented relapse or death. CONCLUSION: MDR-TB is a curable disease in non-HIV-infected patients. Individualised treatment regimens should be based on treatment history and the study of in vitro susceptibility and by promoting a relationship with the patient that makes adherence to treatment easier and minimises side effects.

[Clinical research ethics in respiratory medicine]. / Aspectos éticos de la investigación clínica en neumología.

Clinical research plays an increasingly strong role in the development of respiratory medicine. Familiarity with issues that affect research on human subjects is therefore essential, particularly so with regard to the conduct of clinical trials of medical with medications. This paper begins with a brief introduction to the ethics of clinical research. We highlight the importance of directives on ethics and the need to understand and comply with them when any type of experiment is conducted on humans. Following is a brief description of historical codes of bioethics and an account of their underlying principles, origins, and consequences. Finally, we discuss Spanish Royal Decree 23/2004 of February 6, 2004 which came into force on May 1 that year; we outline its general principles and analyze 2 types of problem that have emerged: those that result from the article requiring a single central opinion and those of investigators who act independently of the pharmaceuticals industry. The situation of clinical research in respiratory medicine at our hospital is then described. Finally, the 7 requirements of ethical research listed by Emanuel and colleagues are proposed as a tool that pneumologists can use to analyze and assess whether or not a specific trial meets minimum ethical requirements.

[The patents game. Generic and biosimilar drugs]. / Juego de patentes. Sobre medicamentos genéricos y biosimilares.

The protection provided by patents on medicines has a limited duration. The expiry of patents expiration allows copies of the drugs to be released, competing with original. At first, they were identical to the original, known as generic drugs, but in recent years, due to the marketing of biological therapies and the expiry of many of their patents, biosimilar drugs have also emerged. These are not exact copies of the original, but, like generic drugs, biosimilar drugs have to demonstrate equivalence to the reference drugs in quality, safety and efficacy. Nevertheless, despite their importance and contribution to sustainability of health system, doctors are sometimes unaware of differences between them, and their impact in terms of clinical and economic effects. An attempt is made to review and clarify certain aspects often unknown by physicians, despite their involvement in their use.

Regulation of breathing and perception of dyspnea in healthy pregnant women.

STUDY OBJECTIVE: To examine if the perception of dyspnea during normal pregnancy may be related to an inappropriate ventilatory response to the increased metabolic rate, due to a higher chemosensitivity. PATIENTS AND INTERVENTIONS: At weeks 12, 24, and 36 of gestation and 4 months after delivery, 11 healthy pregnant women with dyspnea and 12 asymptomatic pregnant women were studied. Progesterone plasma levels, lung volumes, diffusion capacity, maximal respiratory pressures, rest oxygen uptake, breathing pattern, and mouth occlusion pressure (P0.1) were measured. Progressive isocapnic hypoxic stimulation and progressive hyperoxic hypercapnic stimulation were performed. RESULTS: Oxygen ventilation equivalent during pregnancy was significantly higher for the dyspneic group than for nondyspneic pregnant women. Dyspneic patients exhibited greater minute ventilation, tidal volume, and P0.1 than the nondyspneic group. The mean values of ventilatory and P0.1 slopes to hypoxia and CO2 during pregnancy were significantly greater in the patients with dyspnea than in asymptomatic subjects. These changes were not due to differences in progesterone plasma levels. A significant relation among the Borg score, inspiratory drive, and chemosensitivity was found. CONCLUSIONS: In some pregnant women, a higher sensitivity to CO2 and hypoxia may induce excessive ventilation to metabolic demand, which would contribute to dyspnea.

CT in the evaluation of the upper airway in healthy subjects and in patients with obstructive sleep apnea syndrome.

AIM: To study if the caliber of the upper airway, measured by CT, allows us to distinguish patients with obstructive sleep apnea syndrome (OSAS) from healthy people. PATIENTS AND METHODS: Sixteen OSAS patients (with an apnea-hypopnea index > 10) and 39 healthy volunteers were studied. Polysomnography and CT of the upper airways during awake periods were performed in both groups. We used third-generation equipment (Toshiba model TCT 600QT). The area of the nasopharynx, oropharynx, and hypopharynx (in inspiration and expiration), the uvula diameter, and retropharyngeal tissue were evaluated. The simultaneous identification of the variables that differentiate between control and OSAS groups was determined by a multivariate discriminant model. RESULTS: The retropharyngeal tissue in OSAS men was greater than those of the control men (10.3+/-3.6 mm vs 6.4+/-2.7 mm; p < 0.01). The multivariate analysis was performed on the 29 men (14 OSAS and 15 non-OSAS) who had information compiled in the selected parameters. The retropharyngeal tissue, expiratory hypopharynx, and uvular diameter are used to create a discriminant model (Wilks' lambda=0.556; p < 0.01). Two non-OSAS and five OSAS patients were incorrectly classified by this model as members of the other group (total rate of error, 24.14%). Therefore, the point estimates of specificity and sensitivity are 86.67% and 64.29%, respectively, for this model. The Pearson correlation coefficient between body mass index and retropharyngeal tissue is 0.63 (p < 0.001). CONCLUSIONS: CT could play an important role in studying the upper airway in patients with OSAS. The determination of the retropharyngeal tissue by CT could be a useful procedure to evaluate OSAS.

How to express tumor markers in bronchoalveolar lavage.

INTRODUCTION: Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results. OBJECTIVE: The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered. PATIENTS AND METHODS: A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found. RESULTS: We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP. CONCLUSIONS: Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.

Health-related quality of life in patients with obstructive sleep apnea: effects of long-term positive airway pressure treatment.

The aim of the present study was to determine the effect of middle and long-term positive airway pressure (CPAP) treatment on the health-related quality of life in patients with obstructive sleep apnea. We prospectively studied two groups of patients with this disease; a group of 42 patients (33 men and 9 women) with a mean age of 55.2 +/- 7.4 years and a body mass index of 33.5 +/- 6.4 kg/m2 treated with CPAP for 6-months, and another group of 42 patients (34 men and 8 women) with a mean age of 54.4 +/- 10.5 years and a body mass index of 33.2 +/- 4.0 kg/m2 treated with CPAP for 18-months. The health related quality of life was assessed by administering a Medical Outcomes Study Short Form-36 (SF-36) questionnaire before and after CPAP therapy. Patients treated with CPAP for 6 months only improved significantly in the vitality dimension and this change was clinically relevant (standard error of the measurement = 1.43 SEmeas). In contrast, those treated with CPAP for a long period (18-month) showed statistically significant improvement at post-treatment in five SF-36 dimensions: physical functioning (P < 0.001), role physical (P < 0.01), social functioning (P < 0.01), vitality (P < 0.001), and general health perception (P < 0.001). In four of these dimensions the improvement was clinically relevant: role physical (1.16 SEmeas), social functioning (1.35 SEmeas), vitality (1.35 SEmeas), and general health perception (2.05 SEmeas). Using two different global rating of change (independent measures or anchors), the minimal change important difference for patients treated with CPAP for 6 months ranged from 20.7 to 24.2 points on the vitality dimension; and for patients with CPAP for 18-months it ranged from 2.5 to 7.5 points on the physical role, 5.5-6.6 points on social functioning, 7.5-8.7 on vitality, and 13.5-15.5 on general health perception dimension. We conclude that health-related quality of life of obstructive sleep apnea patients improves with long term CPAP treatment and these changes are clinically relevant in several health dimensions.

Usefulness of bronchial reactivity analysis in the diagnosis of bronchial asthma in patients with bronchial hyperresponsiveness.

We examined the usefulness of some bronchial reactivity indices to identify bronchial asthma in patients with airway hyperresponsiveness. Eighty-eight consecutive patients with positive response to histamine bronchial challenge (> or = 20% fall in FEV1) were included in the study. Dose-response curves were characterised by their sensitivity (PD20) and reactivity. Dose-response slope, continuous index of responsiveness (CIR) and bronchial reactivity index (BRI) with respect to baseline and post-diluent baseline values were determined as reactivity indices. The clinical diagnosis remaining in the case history 2 years after the bronchial challenge was considered the definitive diagnosis. Asthmatic patients had higher baseline BRI (12.121+/-0.412 vs. 11.615+/-0.201; P<0.001) and post-diluent baseline BRI (12.054+/-0.368 vs. 11.563+/-0.531; P = 0.003) than other subjects. Area beneath their receiver operating characteristic (ROC) curve was 82.68% (standard error: 0.77) for the baseline BRI and 81.73 (standard error: 0.76). By multiple logistic regression analysis, baseline BRI was the only independent variable identified as a predictor for diagnosis of bronchial asthma (r = 0.387, P = 0.0007). A cut-off of 11.76 for baseline BRI reached an 87.2% sensitivity and an 80% specificity for bronchial asthma diagnosis. In conclusion, BRI calculated with respect to baseline FEV1 should be useful in identifying asthmatic patients among subjects with airway hyperresponsiveness.

Long-term survival in a surgically treated non-encapsulated mediastinal primary liposarcoma. Diagnostic utility of core-needle biopsy for mediastinal tumors.

Primary liposarcomas of the mediastinum are uncommon tumors. Only six cases of mediastinal liposarcomas with survival after surgery longer than five years have been reported and only one of these was a non-encapsulated tumor. We report a new case of non-encapsulated primary liposarcoma of the mediastinum with long-term survival. The diagnosis was carried out using a CT-guided core-needle biopsy. We emphasize the utility of this technique to diagnose this kind of mediastinal tumors. A non-encapsulated primary liposarcoma of the mediastinum surgically treated with long-term survival is reported. We emphasize the diagnostic utility of CT-guided core-needle biopsy for the tumors.