Coexistence of Eosinophilic Granulomatosis With Polyangiitis and Allergic Bronchopulmonary Aspergillosis: A Fascinating Relationship.

Elevated eosinophil counts are associated with various diseases, including eosinophilic granulomatosis with polyangiitis (EGPA) and allergic bronchopulmonary aspergillosis (ABPA). EGPA is a rare small-vessel vasculitis characterized by asthma, eosinophilia, fleeting pulmonary infiltrates, and systemic manifestations. ABPA, initiated by immune reactions against Aspergillus fumigatus in the airways, presents with poorly controlled asthma, wheezing, hemoptysis, productive cough, and systemic symptoms, which result in characteristic central bronchiectasis. Fleeting pulmonary opacities are common radiologic findings. We present a case of ABPA in a patient with a prior EGPA diagnosis under treatment with mepolizumab 300 mg monthly and review eight similar cases from the literature. In these cases, EGPA and ABPA diagnoses preceded each other or were concurrent. Treatment of the latter improved control of both diseases. IL-5 is pivotal in EGPA pathogenesis, and mepolizumab, targeting IL-5, has been effective in EGPA treatment. Our patient received mepolizumab for EGPA and continued it post-ABPA diagnosis, showing favorable outcomes. This suggests mepolizumab as a therapeutic link between EGPA and ABPA. Mepolizumab therapy holds promise for managing both EGPA and ABPA. Double-blind placebo-controlled studies are warranted to establish its efficacy and safety for ABPA, emphasizing the need for further research in this area.

Drivers of habitat availability for terrestrial mammals: Unravelling the role of livestock, land conversion and intrinsic traits in the past 50 years.

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible. We aim to assess the proportions of available habitat within the lost and retained parts of mammals' distribution ranges, and to identify the drivers of habitat availability. We produced distribution maps for 475 terrestrial mammals for the range they occupied 50 years ago and compared them to current range maps. We then calculated the differences in the percentage of 'area of habitat' (habitat available to a species within its range) between the lost and retained range areas. Finally, we ran generalized linear mixed models to identify which variables were more influential in determining habitat availability in the lost and retained parts of the distribution ranges. We found that 59% of species had a lower proportion of available habitat in the lost range compared to the retained range, thus hypothesizing that habitat loss could have contributed to range declines. The most important factors negatively affecting habitat availability were the conversion of land to rangeland and high density of livestock. Significant intrinsic traits were those related to reproductive timing and output, habitat breadth and medium body size. Our findings emphasize the importance of implementing conservation strategies to mitigate the impacts caused by human activities on the habitats of mammals, and offer evidence indicating which species have the potential to reoccupy portions of their former range if other threats cease to occur.

Opportunities and challenges for Common Agricultural Policy reform to support the European Green Deal.

The Common Agricultural Policy (CAP) is the European Union's main instrument for agricultural planning, with a new reform approved for 2023-2027. The CAP intends to align with the European Green Deal (EGD), a set of policy initiatives underpinning sustainable development and climate neutrality in the European Union (EU), but several flaws cast doubts about the compatibility of the objectives of these 2 policies. We reviewed recent literature on the potential of CAP environmental objectives for integration with the EGD: protection of biodiversity, climate change mitigation and adaptation, and sustainable management of natural resources. The CAP lacks appropriate planning measures, furthering instead risks to biodiversity and ecosystem services driven by landscape and biotic homogenization. Funding allocation mechanisms are not tailored to mitigate agricultural emissions, decreasing the efficiency of climate mitigation actions. The legislation subsidies farmers making extensive use of synthetic inputs without adequately supporting organic production, hindering the transition toward sustainable practices. We recommend proper control mechanisms be introduced in CAP Strategic Plans from each member state to ensure the EU is set on a sustainable production and consumption path. These include proportional assignment of funds to each CAP objective, quantitative targets to set goals and evidence-based interventions, and relevant indicators to facilitate effective monitoring of environmental performance. Both the CAP and the EGD should maintain ambitious environmental commitments in the face of crisis to avoid further degradation of the natural resources on which production systems stand.

Oportunidades y retos para la reforma a la Política Agrícola Común que respalden el Pacto Verde Europeo Resumen La Política Agrícola Común (PAC) es el principal instrumento de planificación agraria de la Unión Europea, con una nueva reforma aprobada para 2023-2027. La PAC pretende alinearse con el Pacto Verde Europeo (PVE), un conjunto de iniciativas políticas que apuntan al desarrollo sostenible y la neutralidad climática en la UE, aunque varias fallas han arrojado dudas sobre la compatibilidad de los objetivos de estas dos políticas. Revisamos la bibliografía reciente sobre el potencial de integración de los objetivos medioambientales de la PAC con el PVE en tres categorías: protección de la biodiversidad; mitigación del cambio climático y adaptación al mismo y, gestión sostenible de los recursos naturales. Encontramos que la PAC carece de medidas de planificación adecuadas, lo que agrava los riesgos para la biodiversidad y los servicios ambientales derivados de la homogeneización biótica y paisajística. Los mecanismos de asignación de fondos no están adaptados para mitigar las emisiones agrícolas, lo que disminuye la eficiencia de las acciones de mitigación del cambio climático. La legislación subsidia a los agricultores que hacen un uso extensivo de insumos sintéticos sin apoyar adecuadamente la producción ecológica, obstaculizando la transición hacia prácticas sostenibles. Recomendamos que se introduzcan mecanismos de control adecuados en los Planes Estratégicos de la PAC de cada Estado miembro para garantizar que la UE se encamina hacia una producción y un consumo sostenibles. Estos mecanismos incluyen la asignación proporcional de fondos a cada objetivo de la PAC, objetivos cuantitativos para fijar metas e intervenciones basadas en pruebas, e indicadores pertinentes para facilitar un seguimiento eficaz de los resultados medioambientales. Tanto la PAC como el PVE deben mantener compromisos medioambientales ambiciosos frente a la crisis para evitar una mayor degradación de los recursos naturales sobre los que se asientan los sistemas de producción.

Global correlates of range contractions and expansions in terrestrial mammals.

Understanding changes in species distributions is essential to disentangle the mechanisms that drive their responses to anthropogenic habitat modification. Here we analyse the past (1970s) and current (2017) distribution of 204 species of terrestrial non-volant mammals to identify drivers of recent contraction and expansion in their range. We find 106 species lost part of their past range, and 40 of them declined by >50%. The key correlates of this contraction are large body mass, increase in air temperature, loss of natural land, and high human population density. At the same time, 44 species have some expansion in their range, which correlates with small body size, generalist diet, and high reproductive rates. Our findings clearly show that human activity and life history interact to influence range changes in mammals. While the former plays a major role in determining contraction in species' distribution, the latter is important for both contraction and expansion.

Geographic distribution ranges of terrestrial mammal species in the 1970s.

Here we provide geographic distribution ranges for 205 species of terrestrial non-volant mammals in the 1970s. We selected terrestrial non-volant mammals because they are among the most studied groups, have greater availability of historical distribution data for the 1970s decade, and also show the largest range contractions compared to other taxonomic groups. Species belong to 52 families and 16 orders. Range maps were extracted from scientific literature including published papers, books, and action plans. For Australian species, due to the absence of published maps, we collated occurrence data from individual data sets (maintained by museums and government agencies) and converted these into polygonal range maps. Taxonomic and geographic biases towards more studied (charismatic) species are inevitably present. Among the most abundant orders, the highest percentage representation is for Carnivora (55 species, corresponding to 21% of species in the order), Cetartiodactyla (24 species, 10% of the order), and Perissodactyla (six species, 38% of the order). In contrast, the percentage representation is low for Rodentia (66 species, 3% of species in the order), Primates (19 species, 4%), and Eulipotyphla (6 species, 1%). The proportional representation of less speciose orders is highly variable. The data set offers the opportunity to measure the recent (1970-2019) change in the distribution of terrestrial mammal species, and test ecological and biogeographical hypotheses about such change. It also allows us to identify areas where changes in species distribution were largest. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper.

Rationale underlying the measurement of fractional exhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterised by tissue fibrosis leading to vascular injury. Nitric oxide (NO) has been implicated in the pathogenesis of autoimmune diseases. A deficiency in basal NO production by the constitutive endothelial isoform of nitric oxide synthase may promote vasoconstriction and vascular wall thickening. In January 2017, we searched the PubMed/Medline, Cochrane Library and Enbase/Medline databases for studies analysing physio-pathological correlations with lung fractional exhaled NO (FeNO) production. This review describes the rationale underlying possible applications of FeNO measurements in the management of SSc. Measuring NO levels at multiple expiratory flow rates makes it possible to distinguish airway NO production and distal airway/alveolar NO concentration (ANOC), and there is increasing evidence indicating that it may be useful in many non-respiratory conditions. FeNO levels are increased in SSc patients with fibrosing lung disease, whereas those with pulmonary hypertension have relatively low FeNO levels, thus suggesting that NO plays an important role in regulating pulmonary vascular resistance in SSc. However, a number of studies have shown increased ANOC in SSc patients without increased FeNO levels. The relationship between lung diffusing capacity for carbon monoxide and ANOC may be related to increased alveolar membrane thickness impeding NO diffusion or alveolar inflammation in SSc lung disease. The findings concerning the usefulness of FeNO measurements in SSc patients are discordant, but the available papers suggest that ANOC is a more accurate indicator of progressive lung dysfunction and an increase in ANOC could assess the extent of interstitial lung disease non-invasively.

Psoriasis and Respiratory Comorbidities: The Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy.

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

Performance of the Flash Glucose Monitoring System during exercise in youth with Type 1 diabetes.

AIM: Metabolic changes during exercise may affect the accuracy of glucose sensors impacting on Type 1 diabetes (T1D) management. The present study aimed at assessing the performance of the Flash Glucose Monitoring system (isCGM) during exercise and in free-living condition in youth with T1D. METHODS: Seventeen youth (53% male), aged 13.7 ±â€¯3.8 years, with T1D for 5.4 ±â€¯3.8 years, HbA1c 7.4 ±â€¯1.0% (57 ±â€¯11 mmol/mol), were enrolled. Paired isCGM, plasma (PG) and capillary (CG) glucose values (total of 136) were collected during an interval exercise (45 min at 55% VO2max load with 20 s sprints at 80% VO2max every 10 min). Paired isCGM and CG (total of 832) were collected during free-living condition. RESULTS: During exercise, isCGM absolute relative difference (ARDs) means/medians were 12.5/9.4% versus PG and 15.4/10.8% versus CG. During rest, ARDs means/medians were 16.6/12.0%. The Consensus Error Grid analysis showed 98.4% of readings during exercise and 97.24% during rest in zones A + B. Percentage of readings meeting the ISO criteria for CG levels <5.55 mmol/L was 62.5% during exercise, 53.4% during rest; for CG levels ≥5.55 mmol/L was 64.0% during exercise, 60.4% during rest. CONCLUSIONS: isCGM demonstrated similar clinical safety and performance during exercise and in everyday life; further studies are needed to confirm its accuracy during exercise.

Usefulness of six-minute walk test in systemic sclerosis.

The 6-minute walk test (6MWT) is a standardised, feasible and reliable measure of sub-maximal exercise capacity that has never been fully validated in systemic sclerosis (SSc). A variety of data suggest that many non-pulmonary aspects of SSc contribute to the test results, thus blunting the ability of the 6MWT to measure changes in lung function. Sources of variability are a training effect, technician experience, subject encouragement, medication, other activities on day of testing, deconditioning and the effects of musculoskeletal conditions and pain. Another cause of variability is the anatomical site the probe is attached to: a forehead probe is preferable to a finger or earlobe sensor. The indiscriminate use of the 6MWT for all SSc patients is not useful. It should be used in patients with pulmonary involvement, combined with diffusion capacity of the lung for carbon monoxide (DLCO) and its components (membrane diffusion and capillary volume) or the Sclerodermia Health Assessment Questionnaire Disability Index. The use of these combined parameters may indicate the onset of pulmonary hypertension. Recent studies suggest two alternatives to the 6MWT: maximal cardiopulmonary exercise testing and DLCO testing during effort. However, their use must still be validated.

Role of nebulized glycopyrrolate in the treatment of chronic obstructive pulmonary disease.

In the upcoming years, the proportion of elderly patients with chronic obstructive pulmonary disease (COPD) will increase, according to the progressively aging population and the increased efficacy of the pharmacological treatments, especially considering the management of chronic comorbidities. The issue to prescribe an appropriate inhalation therapy to COPD patients with significant handling or coordination difficulties represents a common clinical experience; in the latter case, the choice of an inadequate inhalation device may jeopardize the adherence to the treatment and eventually lead to its ineffectiveness. Treatment options that do not require particular timing for coordination between activation and/or inhalation or require high flow thresholds to be activated should represent the best treatment option for these patients. Nebulized bronchodilators, usually used only in acute conditions such as COPD exacerbations, could fulfill this gap, enabling an adequate drug administration during tidal breathing and without the need for patients' cooperation. However, so far, only short-acting muscarinic antagonists have been available for nebulization. Recently, a nebulized formulation of the inhaled long-acting muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary vibrating mesh nebulizer closed system (SUN-101/eFlow®), has progressed to Phase III trials and is currently in late-stage development as an option for maintenance treatment in COPD. The present critical review describes the current knowledge about the novel nebulizer technology, the efficacy, safety, and critical role of nebulized glycopyrrolate in patients with COPD. To this end, PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for relevant papers. According to the available results, the efficacy and tolerability profile of nebulized glycopyrrolate may represent a valuable and dynamic treatment option for the chronic pharmacological management of patients with COPD.

Influence of autonomic nervous system dysfunction in the genesis of sleep disorders in fibromyalgia patients.

OBJECTIVES: Fibromyalgia (FM) is characterised by chronic musculoskeletal pain, autonomic nervous system (ANS) dysfunction, and disturbed sleep. The aim of this study was to evaluate the influence of ANS dysfunction on the genesis of sleep disorders. METHODS: Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep. RESULTS: The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest (p<0.05), and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient (p<0.01), and they had a higher proportion of stage 1 non-REM sleep (p<0.001), experienced many arousals and periodic limb movements (PLMs) per hour of sleep (p<0.001) and a high proportion of periodic breathing (PB%) (p<0.0001). Their cyclic alternating pattern (CAP) rate was significantly increased (p<0.001). During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR (p<0.001). The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep. CONCLUSIONS: Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity.

Oxygen therapy in COPD patients with isolated nocturnal hypoxemia; comparison of quality of life and sleep between bronchitis and emphysema phenotype: A prospective observational study.

BACKGROUND: COPD is a heterogeneous disease composed by two main phenotypes: bronchitis (COPDb) and emphysema (COPDe) with different clinical presentation, physiology, imaging, response to therapy and decline in lung function. The aim of this study is to evaluate whether nocturnal hypoxemic COPDb and COPDe have a different behaviour during sleep and the effect of nocturnal oxygen supplementation (nO2LT). MATERIALS AND METHODS: 75 COPDb and 120 COPDe were enrolled. All patients performed polysomnography, Pittsburgh and Maugeri Foundation Respiratory Failure questionnaire, and pulmonary function before and after six months of nO2LT. RESULTS: At baseline, compared to COPDb, COPDe have decreased sleep efficiency (SE) (67.5±6% vs. 76.9±3% p<0.05) and higher arousals (A/I) (18.1±3 event/h vs. 8.7±1 event/h p<0.05). Oxygen desaturation index (ODI) was increased during REM (7.1±1 event/h vs. 2.3±0.5 event/h p<0.05). nO2LT in COPDe improves SE (77±4% vs. 67.5±6% p<0.05) and decreases A/I (9±5 event/h vs. 18.1±3 event/h p<0.05). ODI during REM (3.5±2 event/h vs. 7.1±1 p<0.05) decreases and quality of life (QoL) improves (MFR-28 total 56±22 vs 45±20 p<0.05), due to an improvement in cognitive abilities (45±30 vs 33±31 p<0.05) and daily activities (61±29 vs 53±21 p>0.05). In COPDb nO2LT reduces ST90 (15±6% vs. 43±8% p<0.05) less than in COPDe (15±6% vs. 8±4% p<0.05); improves A/I (10±2 event/h vs. 8.7±1 p<0.05) and there is no evidence of an improvement in QoL. CONCLUSIONS: Six months of nO2LT improve quality of life in COPDe, not in COPDb. We found a difference in sleep quality between COPDe and COPDb.

A new approach to detect early lung functional impairment in very light smokers.

PURPOSE: The aim of our study is to investigate if lung carbon monoxide diffusing capacity (DLCO) measured during effort is able to detect early respiratory functional impairment. METHODS: We enrolled 25 very light smokers and 20 healthy non smokers. Subjects underwent plethysmography, DLCO (single breath technique) and calculated effective pulmonary blood flow (Qc) by rebreathing method. During exercise by cycle ergometer (duration 10±2min; recovery 11±3min) DLCO and Qc were calculated at 25% and 50% of theoretical maximum workload. RESULTS: At baseline lung function and Qc did not differ between groups. DLCO and DLCO/Qc measured during exercise were significantly greater in non smokers (p<0.001); Qc was not statistically different. In very light smokers, DLCO, DLCO/Qc measured during exercise significantly correlated with the number of pack years (r=-0.60 p<0.001; r=-0.58 p<0.05; r=-0.55 p<0.05, respectively). CONCLUSIONS: In very light smokers there is lung function impairment and our data show that DLCO during exercise may reveal this underlying early damage.

Diffusing Pulmonary Capacity Measured During Effort: A Possible Early Marker of Pulmonary Involvement In Systemic Sclerosis.

BACKGROUND: Interstitial lung involvement is common and potentially limits the quality of life in patients with systemic limited sclerosis (SScl). OBJECTIVES: To study the lung carbon monoxide diffusion (DLCO) measured during effort in order to identify a possible subclinical impairment. METHODS: We enrolled 20 SScl patients without interstitial lung involement and 20 healthy controls. At enrolment all subjetcs underwent plethysmography, DLCO by single-breath technique, and evaluation of pulmonary blood flow (Qc) with the rebreathing CO2 method. Skin involvement in the SScl patients was rated using the modified Rodman skin score (mRSS). During exercise on a cycle ergometer, DLCO, DLCO/ alveolar volume (Kco) and Qc were calculated at 25% and 50% of predicted maximum workload (25% pmw and 50% pmw). RESULTS: At baseline two groups did not differ in age, body mass index, lung function or Qc. In the controls, DLCO, Kco and DLCO/Qc measured at 25% pmw and 50% pmw were significantly higher than in SScl patients, while Qc was not different. Based on response to effort, SScl patients were divided into two groups: responders, with an increase of DLCO(25%pmw) and DLCO(50%pmw) at least 5% and 10% respectively, and non-responders. The non-responders showed greater skin involvement and significantly reduced DLCO, Kco and DLCO/Qc values at rest than responders. CONCLUSIONS: Moderate effort in SScl patients may reveal a latent impairment in gas diffusion through the alveolar/capillary membrane, thus confirmig that exertional DLCO can identify lung damage at an earlier stage than DLCO at rest.