Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Survey of the Radioguided Surgery Working Group (GTCRG-RGSWG) of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM): Radioguided localization of non-palpable breast lesions with or without indication for selective sentinel node biopsy: ROLL, SNOLL and 125I seeds.

OBJECTIVE: To know the current status of the technique of radioguided localisation of non-palpable breast lesions with or without indication for selective sentinel node biopsy -ROLL, SNOLL and 125I seeds- by conducting a national survey developed by the Working Group on Radioguided Surgery (GTCRG) of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM). MATERIAL AND METHODS: In October 2020, the form was sent in digital format to the different nuclear medicine services in Spain. A response time of 2 months with an overtime of 15 days was given. The number of ROLL/SNOLL procedures in each centre and the methodology used were obtained, including important technical details. In addition, a specific section on 125I seeds was included. The results were automatically downloaded into an Excel 2007 spreadsheet for subsequent analysis with the same program. RESULTS: The survey was answered by 55 centres; 21 use wire-guided localisation while the remaining 34 use different radioguided surgery techniques (RGS) for the localisation of non-palpable breast lesions, with the results itemized into thirteen sections. The commonly used tracer dose is 111 MBq for the ROLL technique and 222 MBq for the SNOLL technique, with a volume of 0.2 ml. The most common protocol is the two-day protocol. 26% of centres performing CRG use 125I seeds for both breast lesion and suspicious/pathological node detection, with the time between implantation and removal being about 3 days, with subsequent radiological control in most cases. CONCLUSION: The survey shows the relevance of radioguided surgery in the management of breast cancer patients at different stages of the disease, with disparity in the implementation of new techniques and tools, which responds to the multiple healthcare realities of Nuclear Medicine services.

Should we consider paranasal and chest computed tomography in severe asthma patients?

BACKGROUND: It is essential to recognize and treat findings that can simulate or worsen symptoms to improve asthma control and thereby to reduce costs. Guidelines highlight a paranasal (PS) and chest computed tomography (CT) scan as a tool for disease evaluation and, although they suggest its indication in patients whom presentation is atypical, there are not well-defined criteria. OBJECTIVES: To describe the most common findings in the PS and chest CT in severe asthma patients and to analyse the characteristics of asthmatics with the finding of nasal polyps or bronchiectasis. METHODS: We retrospectively reviewed the medical records of 161 adults with confirmed severe asthma who had undergone to PS and/or chest CT. Clinical data from their electronic health record and the findings from a PS and/or chest CT within the last five years were collected. RESULTS: In the PS CT, 70.5% of patients presented mucous thickening and 46.7% presented nasal polyps. Both findings were associated with male gender and level of blood eosinophils. In chest CT, 28% of individuals showed atelectasis, 16.5% air trapping, 17.7% affectation of the small airway, 11.6% pulmonary infiltrates and 10.4% emphysema. Bronchiectasis were identified in 60.4% of subjects, who were older and had poorer lung function. CONCLUSION: Paranasal and thoracic computed tomography are important tools in the treatment of severe asthma because they allow us to detect highly prevalent findings in this disease that can lead to poorer control of it.

Obesity and Asthma: Key Clinical Questions.

Obesity is a common comorbidity of asthma that is associated not only with development of the disease, but also with poorer disease control and greater severity. Recent prospective evidence supports the idea that body weight gain precedes the development of asthma, although the debate is far from over. The objective of this document is to conduct a systematic review of 3 clinical questions related to asthma and obesity: (a) Obesity and asthma: the chicken or the egg? Clinical insights from epidemiological and phenotyping studies. (b) Is obesity a confounding factor in the diagnosis and management of asthma, especially in severe or difficult-to-control asthma? (c) How do obese asthma patients respond to pharmacological treatments and to biological drugs? Do we have effective specific interventions? Revised epidemiological, pathological, and mechanistic evidence combined with data from interventional clinical trials prevent us from clearly stating that obesity causes asthma. However, the complexity and heterogeneity of both illnesses make several clinical scenarios possible. Furthermore, asthma represents an additional clinical challenge in the obese patient. Physicians need to be aware of the confounding effects created by the more marked perception of symptoms, alterations in lung function, and the various comorbidities that obese persons present. Exhaustive phenotyping of the obese asthma patient should enable us to develop a rational therapeutic plan, including both the pharmacological approach and specific antiobesity therapies such as combining diet and exercise and, in extreme cases, bariatric surgery.

Update on radioguided surgery: from international consensus on sentinel node in head and neck cancer to the advances on gynaecological tumors and localization of non-palpable lesions. / Actualización en cirugía radioguiada: del consenso internacional en ganglio centinela de cabeza y cuello a los avances en tumores ginecológicos y localización de lesiones no palpables.

The aim of this review is to provide an updated perspective on different fields of radioguided surgery. With reference to the sentinel lymph node biopsy in oral squamous cell carcinoma, we present the results of the interactive debate held at the recent Congress of our specialty about the more relevant aspects of the London Consensus. Drainage peculiarities and indications according to the current guidelines on gynaecological tumours, endometrial and cervical cancer, are detailed and new scenarios for nuclear medicine physicians are presented; robotic surgery and hybrid tracers, for instance. Moreover, the notable growth in radioguided surgery indications for non-palpable lesions, widely used in mammary pathology, make it advisable to update two procedures which have shown satisfying results, such as the solitary pulmonary nodule and the osteoid osteoma.

Eosinophil-derived exosomes contribute to asthma remodelling by activating structural lung cells.

BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesized that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals. All experiments were performed with eosinophil-derived exosomes from healthy and asthmatic subjects. Epithelial damage was evaluated using primary small airway epithelial cell lines through 2 types of apoptosis assays, that is, flow cytometry and TUNEL assay with confocal microscopy. Additionally, the epithelial repair was analysed by performing wound healing assays with epithelial cells. Functional studies such as proliferation and inhibition-proliferation assays were carried out in primary bronchial smooth muscle cell lines. Also, gene expression analysis of pro-inflammatory molecules was evaluated by real-time PCR on epithelial and muscle cells. Lastly, protein expression of epithelial and muscle cell signalling factors was estimated by Western blot. RESULTS: Asthmatic eosinophil-derived exosomes induced an increase in epithelial cell apoptosis at 24 hour and 48 hour, impeding wound closure. In addition, muscle cell proliferation was increased at 72 hours after exosome addition and was linked with higher phosphorylation of ERK1/2. We also found higher expression of several genes when both cell types were cultured in the presence of exosomes from asthmatics: CCR3 and VEGFA in muscle cells, and CCL26, TNF and POSTN in epithelial cells. Healthy eosinophil-derived exosomes did not exert any effect over these cell types. CONCLUSIONS AND CLINICAL RELEVANCE: Eosinophil-derived exosomes from asthmatic patients participate actively in the development of the pathological features of asthma via structural lung cells.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

Anticancer drug design using scaffolds of ß-lactams, sulfonamides, quinoline, quinoxaline and natural products. Drugs advances in clinical trials.

Eleven years after the start of a new millennium characterized by amazing scientific development, the cure for cancer remains a major challenge for humanity. In this regard, scientific efforts have focused on the search for new therapeutic targets that involve specific recognition and stop the spread of cancer cells, as well as the development of new therapeutic options that show greater specificity and better therapeutic efficacy. This review includes recent published literature about new anticancer drug design using scaffolds of ß-lactams, sulfonamides, quinoline, quinoxaline and natural products, and focuses on the structure-activity relationships of scaffolds that have been reported to potently inhibit cell growth of human tumor cell lines. It describes not only those synthetic or natural compounds aimed at specific molecular targets of cancer cells in vitro, but also compounds currently in clinical trials.

[Asthma, obesity and diet]. / Asma, obesidad y dieta.

Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous studies have linked both disorders. Most prospective studies show that obesity is a risk factor for asthma and have found a positive correlation between baseline body mass index (BMI) and the subsequent development of asthma, although these results are not conclusive when studying the association between airway hyperresponsiveness with BMI. Furthermore, several studies suggest that whereas weight gain increases the risk of asthma, weight loss improves the course of the illness. Different factors could explain this association. Obesity is capable of reducing pulmonary compliance, lung volumes and the diameter of peripheral respiratory airways as well as affecting the volume of blood in the lungs and the ventilation-perfusion relationship. Furthermore, the increase in the normal functioning of adipose tissue in obese subjects leads to a systemic proinflammatory state, which produces a rise in the serum concentrations of several cytokines, the soluble fractions of their receptors and chemokines. Many of these mediators are synthesized and secreted by cells from adipose tissue and receive the generic name of adipokines, including IL-6, IL-10, eotaxin, TNF-α, TGF- 1, PCR, leptin y adiponectin. Finally, specific regions of the human genome which are related to both asthma and obesity have been identified. Most studies point out that obesity is capable of increasing the prevalence and incidence of asthma, although this effect appears to be modest. The treatment of obese asthmatics must include a weight control program.

Diagnosis of aspirin-induced asthma combining the bronchial and the oral challenge tests: a pilot study.

BACKGROUND: We investigated the usefulness of the bronchial challenge (BC) with lysine-acetylsalicylate (L-ASA) in the diagnosis of aspirin-exacerbated respiratory disease (AERD) using a protocol that combined both the oral challenge (OC) and the BC tests. METHODS: Adult asthmatic patients with suspected AERD who underwent BC with L-ASA were included in the study. If the BC result with L-ASA was negative, an OC was carried out to establish the diagnosis. AERD was ruled out if both the BC and the OC results were negative (nonresponders). Both responders and nonresponders were compared for age, gender, a personal or family history of atopy, underlying disease, current asthma treatment, and presence of nasal polyps. Six patients with asthma but no suggestive history of AERD were included as controls. RESULTS: Twenty-two patients completed the study. Ten patients tested positive to the BC and/or OC (responders), whereas 12 did not (nonresponders). Seven out of the 10 responders had a positive BC result and 3 a positive OC result. After BC, 4 patients had an early asthmatic response, 1 had a dual response, and 2 had isolated late responses. No significant differences were observed in the aforementioned variables between responders and nonresponders. The results of both challenges were negative in the 6 controls. CONCLUSIONS: The BC had a high positive predictive value, was safe, and when negative, the subsequent OC did not result in any severe adverse reactions. The BC elicited an isolated late asthmatic response that has not been previously described in the literature.

Obesity and asthma.

Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous studies have linked these disorders. Most prospective studies show that obesity is a risk factor for asthma and have found a positive correlation between baseline body mass index and the subsequent development of asthma. Furthermore, several studies suggest that whereas weight gain increases the risk of asthma, weight loss improves the course of the illness. Different factors could explain this association. Obesity is capable of reducing pulmonary compliance, lung volumes, and the diameter of peripheral respiratory airways as well as affecting the volume of blood in the lungs and the ventilation-perfusion relationship. Furthermore, the increase in the normal functioning of adipose tissue in obese subjects leads to a systemic proinflammatory state, which produces a rise in the serum concentrations of several cytokines, the soluble fractions of their receptors, and chemokines. Many of these mediators are synthesized and secreted by cells from adipose tissue and receive the generic name of adipokines, including IL-6, IL-10, eotaxin, tumor necrosis factor-alpha, transforming growth factors-beta1, C-reactive protein, leptin, and adiponectin. Finally, specific regions of the human genome related to both asthma and obesity have been identified. Most studies point out that obesity is capable of increasing the prevalence and incidence of asthma, although this effect appears to be modest. The treatment of obese asthmatics must include a weight control program.

[Usefulness of bone scintigraphy for staging in a case of histiocytosis of the temporal bone]. / La gammagrafía ósea demuestra ser útil para el diagnóstico de extensión en un caso de histiocitosis X del hueso temporal.

We present the case of a 43-year-old man diagnosed of insipid diabetes and hypogonadotropic hypogonadism in whom a right temporal bone lesion was observed in the control MRI, thus leading to his admission. A bone scintigraphy with 99mTc-HMDP showed increased uptake in the right temporal region with sphenoidal extension, coinciding with the MRI. In addition, increased uptake having less intensity and size was observed in the left temporal region. A biopsy on the newly appearing mouth ulcers in the jugal mucous was performed and showed Langerhan's cells, the diagnosis of histiocytosis X being confirmed. Six months later a new MRI indicated disease progression with bilateral temporal involvement. The bone scan findings in this case provided a more exact extension diagnosis of the disease than the MRI.

[Usefulness of pilocarpine in the prevention of xerostomia in patients with head and neck cancer treated with radiotherapy. Assessment with gammagraphy and salivary flow]. / Utilidad de la pilocarpina como profiláctico de xerostomía en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Valoración mediante gammagrafía y flujo salivar.

AIM: To assess the utility of salivary gland scintigraphy and salivary flow to quantify salivary function and to evaluate the usefulness of pilocarpine in the treatment of radiation-induced xerestomia in head and neck cancer patients. METHOD: Thirty two patients with head and neck tumor treated with radiotherapy (RDT) were studied. Patients were classified into two groups: pilocarpine group (P), that received prophylactic pilocarpine before RDT and during the first year after treatment. No pilocarpine group (NP) that received RDT without pilocarpine. Salivary gland scintigraphy and salivary flow were performed before RDT and during one year after treatment. Parotid and submaxillary uptake and excretion were calculated. Salivary flow after stimulation during five minutes was also obtained. RESULTS: Uptake and excretion in both salivary glands decreased after RDT. There were no statistical differences comparing P and NP groups (p < 0.001). However, in group P a trend to recovery was observed in parotid uptake values at 12 months after treatment, but it was not statistically significant. In both groups the salivary flow decreased after RDT and a good correlation (r = 0.8) between salivary flow and submaxillary excretion and parotid excretion was found. CONCLUSIONS: Salivary gland scintigraphy and salivary flow could be useful to evaluate salivary gland function in patients with head and neck irradiated tumors. Although better results on the salivary uptake at 12 months were noted, pilocarpine did not significantly improve salivary gland function.

Exposure to parakeets and bronchiolitis obliterans.

Case report of a 64-year-old woman with increasing dyspnea and cough. She cared at home for 8 parakeets (Melopsittacus undulatus). Subsequent studies revealed a restrictive pulmonary defect and transbronchial biopsy, a histological bronchiolitis obliterans (BO). No significant elevated anti-avian IgG could be detected, probably because of a transient hypogammaglobulinaemia. The implication of antigenic exposure to avian antigens in the pathogenesis of BO is discussed.

Gastric anisakiasis: an underestimated cause of acute urticaria and angio-oedema?

Acute urticaria and angio-oedema are common in primary care and in the emergency unit. Food allergy is one possible cause. We describe gastric anisakiasis, in which symptoms are often not obviously related to eating raw fish. A study was made of patients presenting at the emergency department who had allergic symptoms such as urticaria or angio-oedema and had recently eaten raw or undercooked fish. They were divided into two groups. Patients in group A (n = 13) also had abdominal symptoms and were diagnosed as having gastric anisakiasis by fibre-optic gastroscopy where third-stage larvae of Anisakis simplex were visualized and extracted. Skin prick tests and specific IgE to A. simplex were positive. Patients in group B (n = 13) had only allergic symptoms after eating raw fish. Eleven of 13 patients had positive skin prick tests and specific IgE to A. simplex. Three of 15 control subjects had positive skin prick tests and specific IgE to A. simplex. Allergic symptoms appeared from 2 to 20 h (mean 5.0) after ingestion in group A and from 20 min to 23 h (mean 4.3 h) in group B. Gastric symptoms in group A disappeared rapidly after extraction of the larvae. Allergic symptoms disappeared in most cases within the first 24 h. We suggest that the allergic symptoms in group A as well as in group B were mainly due to parasitization by A. simplex in sensitized patients. Gastric anisakiasis may be a widely underdiagnosed clinical entity.