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.

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.

Spanish multidisciplinary consensus on the characteristics of severe asthma patients on biologic treatment who are candidates for at-home administration.

BACKGROUND AND OBJECTIVE: Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified. MATERIALS AND METHODS: This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital. RESULTS: One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team's indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly. CONCLUSION: Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice.

Validity of lung ultrasound to rule out iatrogenic pneumothorax performed by pulmonologists without experience in this procedure.

INTRODUCTION: Ultrasonography has been shown to be a useful tool for diagnosing pneumothorax in the hands of experts. After performing bronchopleural procedures, the recommendation is to perform chest radiography to rule out complications. Our objective was to determine the validity of lung ultrasound, conducted by pulmonologists without experience in this procedure, to tule out pneumothorax after invasive procedures. MATERIAL AND METHODS: Our prospective observational study consecutively included patients who underwent transbronchial lung biopsy (TBLB), therapeutic thoracentesis (TT) and/or transparietal pleural biopsies (PB) for whom subsequent chest radiography to rule out complications was indicated. In all cases, the same pulmonologist who performed the technique performed an ultrasound immediately after the procedure. A diagnosis of pneumothorax was considered in the presence of a lung point or the combination of the following signs: absence of pleural sliding, absence of B-lines and presence of the "barcode" sign. RESULTS: We included 275 procedures (149 TBLBs, 36 BPs, 90 TTs), which resulted in 14 (5.1%) iatrogenic pneumothoraxes. Ultrasonography presented a sensitivity of 78.5%, a specificity of 85% and positive and negative predictive value of 22% and 98.6%, respectively. Ultrasonography did not help detect the presence of 3 pneumothoraxes, one of which required chest drainage, but adequately diagnosed 2 pneumothoraxes that were not identified in the initial radiography. CONCLUSIONS: Lung ultrasound performed by pulmonologists at the start of their training helps rule out pneumothorax with a negative predictive value of 98.6%, thereby avoiding unnecessary radiographic control studies in a considerable number of cases.

Validity of thoracic ultrasonography to rule out iatrogenic pneumothorax performed by pulmonologists without experience in this procedure. / Validez de la ecografía torácica para descartar neumotórax iatrogénico realizada por neumólogos sin experiencia en este procedimiento.

INTRODUCTION: Ultrasonography has been shown to be a useful tool for diagnosing pneumothorax in the hands of experts. After performing bronchopleural procedures, the recommendation is to perform chest radiography to rule out complications. Our objective was to determine the validity of thoracic ultrasonography to rule out pneumothorax after invasive procedures, conducted by pulmonologists without experience in this procedure. MATERIAL AND METHODS: Our observational prospective study consecutively included patients who underwent transbronchial biopsy (TBB), evacuating thoracentesis (ECT) and/or transparietal pleural biopsies (TPB) who were indicated subsequent chest radiography to rule out complications. In all cases, the same pulmonologist who performed the technique performed an ultrasound immediately after the procedure. A diagnosis of pneumothorax was considered the presence of a lung point or the combination of the following signs: absence of pleural sliding, absence of B-lines and presence of the «barcode¼ sign. RESULTS: We included 275 procedures (149 TBBs, 36 TPBs, 90 ECTs), which resulted in 14 (5.1%) iatrogenic pneumothoraxes. Ultrasonography presented a sensitivity of 78.5%, a specificity of 85% and a positive and negative predictive value of 22% and 98.6%, respectively. Ultrasonography did not help detect the presence of 3 pneumothoraxes, one of which required chest drainage, but adequately diagnosed 2 pneumothoraxes that were not identified in the initial radiography. CONCLUSIONS: Thoracic ultrasonography performed by pulmonologists at the start of their training helps rule out pneumothorax with a negative predictive value of 98.6%, thereby avoiding unnecessary radiographic control studies in a considerable number of cases.

Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice.

BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.

Social and clinical predictors associated with prolonged hospital stays for patients with severe exacerbation of chronic obstructive pulmonary disease. / Predictores sociales y clínicos asociados con estancia hospitalaria prolongada en pacientes con agudización grave de EPOC.

OBJECTIVE: To determine whether there are social factors that affect the prolonged hospital stay (PHS) of patients with severe chronic obstructive pulmonary disease exacerbation (COPDE), as well as clinical-demographic factors. METHODOLOGY: We conducted a prospective cohort study that consecutively included patients who were admitted to a Pneumology department for COPDE. We recorded demographic, clinical (tobacco use, exacerbations and infections, dyspnoea, impact according to CAT questionnaire, pulmonary function, comorbidities, oxygen therapy and noninvasive ventilation) and social (financial status, caregiver availability and overload, dependence for basic and instrumental activities, social risk and use of social services) variables, employing questionnaires and indices such as Barthel, Lawton-Brody, Zarit, Barber and Gijón. We performed a univariate and multivariate analysis using a logistic regression model. RESULTS: The study included 253 patients, with a mean age of 68.9±9.8years; 77.1% of whom were men. The logistic regression model included active tobacco use, FEV1 value, CAT score >10, dyspnoea 3-4 on the MMRC, the presence of bacteria in sputum cultures, cardiovascular comorbidity, anaemia, home oxygen therapy, living alone, rural residence, caregiver overload and detecting social-family risks/problems. The variables independently associated with the possibility of PHS were a CAT score >10 (OR, 8.9; P=.04) and detecting a social-family risk/problem (OR, 2.6; P=.04). Active smoking was a predictor of shorter stays (OR, 0.15; P=.002). CONCLUSIONS: Variables related to the social sphere play a relevant role in hospital stays, as do the impact of the disease and the persistent use of tobacco by patients with severe COPD exacerbation.

Food Allergies Caused by Allergenic Lipid Transfer Proteins: What Is behind the Geographic Restriction?

PURPOSE OF REVIEW: To critically examine evidence suggesting that food allergy induced by lipid transfer proteins (LTPs) follows a geographic pattern. RECENT FINDINGS: LTP syndrome remains most common in the Mediterranean basin, with a clear gradient seen in prevalence of LTP sensitization between northern and southern Europe. We hypothesize that high levels of birch pollen seem to protect against LTP allergy, as these higher levels correlate with a lower prevalence of LTP hypersensitivity. Nevertheless, LTP food allergy cases still appear in areas having a high environmental level of birch pollen. Food allergy caused by LTP may be related to (1) primary sensitization to a food LTP allergen in the absence of pollinosis, (2) primary sensitization to LTP from a pollen source, and (3) co-sensitization to LTP from pollen and food.

Understanding the spatial distribution of factors controlling topsoil organic carbon content in European soils.

Soil Organic Carbon (SOC) constitutes the largest terrestrial carbon pool. The understanding of its dynamics and the environmental factors that influence its behaviour as sink or source of atmospheric CO2 is crucial to quantify the carbon budget at the global scale. At the European scale, most of the existing studies to account for SOC stocks are centred in the fitting of predictive model to ascertain the distribution of SOC. However, the development of methodologies for monitoring and identifying the environmental factors that control SOC storage in Europe remains a key research challenge. Here we present a modelling procedure for mapping and monitoring SOC contents that uses Visible-Near Infrared (VNIR) spectroscopic measurements and a series of environmental covariates to ascertain the key environmental processes that have a major contribution into SOC sequestration processes. Our results show that it follows a geographically non-stationary process in which the influencing environmental factors have different weights depending on the spatial location. This implies that SOC stock modelling should not rely on a single model but on a combination of different statistical models depending on the environmental characteristics of each area. A cluster classification of European soils in relation to those factors resulted in the determination of four groups for which specific models have been obtained. Differences in climate, soil pH, content of coarse fragments or land cover type are the main factors explaining the differences in SOC in topsoil from Europe. We found that climatic conditions are the main driver of SOC storage at the continental scale, but we also found that parameters like land cover type influence SOC content found at the local scales in certain areas. Our methodology developed at continental scale could be used in future research aimed to improve the predictive performance of SOC assessments at European scale.

Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT-EXT, a Phase III Randomized Study.

In the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors (BENEFIT-EXT), extended criteria donor kidney recipients were randomized to receive belatacept-based (more intense [MI] or less intense [LI]) or cyclosporine-based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent-to-treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI-treated, 138 of 175 belatacept LI-treated and 108 of 184 cyclosporine-treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625-1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634-1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 mL/min per 1.73 m2 for belatacept MI, belatacept LI and cyclosporine, respectively (p < 0.001 for overall treatment effect). HRs comparing freedom from death, graft loss or eGFR <20 mL/min per 1.73 m2 were 0.754 (95% CI 0.536-1.061; p = 0.10) for belatacept MI versus cyclosporine and 0.706 (95% CI 0.499-0.998; p = 0.05) for belatacept LI versus cyclosporine. Acute rejection rates and safety profiles of belatacept- and cyclosporine-based treatment were similar. De novo donor-specific antibody incidence was lower for belatacept (p ≤ 0.0001). Relative to cyclosporine, belatacept was associated with similar death and graft loss and improved renal function at 7 years after transplant and had a safety profile consistent with previous reports.

Islet Amyloid in Whole Pancreas Transplants for Type 1 Diabetes Mellitus (DM): Possible Role of Type 2 DM for Graft Failure.

Long-term results with whole pancreas (WPTx) and islet transplantation (IT) continue to be suboptimal. Graft failure with undetectable C-peptide level is attributed to graft sclerosis (chronic rejection), recurrence of Type 1 diabetes mellitus (DM), or insufficient islet mass. In contrast, graft failure with measurable C-peptide has overlapping clinical features with Type 2 DM (suggesting persistent but insufficient ß cell function), but is poorly understood. In general, the morphological substrate for islet failure is unclear because grafted islets are not routinely evaluated. We present two patients with graft failure at 5 and 8 years after successful WPTx for Type 1 DM, presenting with preserved C-peptide levels. On histopathology, the islets had preserved both α and ß cell populations but also prominent accumulation of islet amyloid (IA), the morphological hallmark of Type 2 DM. IA previously reported in IT, represents fibrillary aggregates of islet amyloid polypeptide, a hormone normally cosecreted with insulin. Accumulation of IA correlates quantitatively with the development of hyperglycemia and is known to cause ß cell dysfunction and loss. Accumulation of IA and development of Type 2 DM should be considered and studied as a potential cause of long-term islet failure in IT and WPTx.