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Summary Background No consensus exists on how to reduce oral corticosteroids after the initiation of biologics in severe asthma. The PONENTE trial evaluated the effectiveness and safety of a rapid, individualised steroid-reduction algorithm, including adrenal insufficiency monitoring, after benralizumab initiation. Methods This multicentre, open-label, single-arm study was done at 138 clinical asthma treatment centres across 17 countries. We enrolled adult patients (age ≥18 years) with severe, eosinophilic asthma (blood eosinophil count ≥150 cells per μL at enrolment or ≥300 cells per μL in the previous year) requiring maintenance oral corticosteroids for at least 3 months preceding enrolment. Patients received benralizumab 30 mg (subcutaneous injection) every 4 weeks for three doses, then every 8 weeks thereafter. The oral corticosteroid reduction phase began at week 4 with daily oral corticosteroid dosages reduced by 1–5 mg every 1–4 weeks depending on the starting dosage, asthma control, and adrenal function status. Adrenal function was assessed with an early morning serum cortisol measurement, followed by adrenocorticotropic hormone stimulation when required, once patients achieved a daily oral corticosteroid dosage of 5 mg/day for 4 weeks. Repeat cortisol measurements were taken for patients with evidence of adrenal insufficiency at first testing. Asthma control was assessed with the Asthma Control Questionnaire-6 (ACQ-6) weekly throughout the induction and oral corticosteroid reduction phases. The primary endpoints were the percentage of patients eliminating daily oral corticosteroids, sustained for at least 4 weeks, and the percentage achieving elimination or a daily prednisone or prednisolone dosage of 5 mg or less, for at least 4 weeks, if the reason for no further reduction was adrenal insufficiency. Safety and efficacy analyses included all patients who received at least one dose of benralizumab and were descriptive. We present results after the oral corticosteroid reduction phase; a maintenance phase is ongoing. The trial is registered with ClinicalTrials.gov , NCT03557307 . Findings Between April 1, 2018, and Sept 5, 2020, of 705 patients assessed for eligibility, 598 were recruited and all received at least one dose of benralizumab. Overall, 376 (62·88%, 95% CI 58·86–66·76) of 598 patients eliminated oral corticosteroids and 490 (81·94%, 78·62–84·94) of 598 eliminated use or achieved a dosage of 5 mg or less if the reason for stopping the reduction was adrenal insufficiency. Subgroup analysis showed that dosage reductions were achieved irrespective of baseline eosinophil count, baseline oral corticosteroid dosage, or oral corticosteroid treatment duration. Adrenal insufficiency was detected in 321 (60%) of 533 patients at first assessment and in 205 (38%) of 533 patients 2–3 months later. The safety profile was consistent with previous experience. Most patients (448 [75%] of 598) had no asthma exacerbations during the oral corticosteroid reduction phase with an annualised exacerbation rate of 0·63. Of 598 patients, 38 (6%) experienced a total of 46 exacerbations resulting in emergency department or urgent care visits or hospitalisations. Interpretation Despite a high prevalence of adrenal insufficiency, most patients with eosinophilic asthma treated with benralizumab achieved elimination of oral corticosteroids or maximal possible reduction using a personalised dosage-reduction algorithm. Funding AstraZeneca.

Background: Some children with asthma experience exacerbations despite long-acting beta2-agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome-wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium. Methods: A meta-analysis of genome-wide association studies (meta-GWAS) was performed in 1,425 children and young adults with asthma (age 6-21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma. Results: Genome-wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta-analysed. Eight independent variants were suggestively (P-value threshold ≤5 × 10−6) associated with exacerbations despite LABA use. Conclusion: No strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short-acting beta2-agonists (SABA). These loci merit further investigation in response to LABA and SABA use.

Under homeostatic conditions, macrophages are the most abundant immune cells in the lung. Pulmonary macrophages are a heterogeneous cell population that can be classified in at least two distinct subpopulations, that is, interstitial macrophages, located within the lung parenchyma, and alveolar macrophages (AM) which reside in the airway lumen, allowing direct contact with the environment (eg, allergens, particulate matter, and commensal bacteria). In recent years, AM have been shown to play an important role in environmental allergen-induced airway inflammation in asthma. Elimination of resident AM resulted in enhanced type 2 airway inflammation in a mouse asthma model, while depletion of blood monocytes resulted in abrogation of newly formed AM after allergen challenge and a decreased type 2 immune response. Knowledge of phenotypic alterations of AM in allergic asthma in humans is limited. In this study, we investigated the effect of house dust mite (HDM) and lipopolysaccharide (LPS) challenge on the transcriptome of AM from patients with mild asthma. We have shown previously that intrabronchial HDM/LPS challenge induces a mixed eosinophilic and neutrophil airways inflammation in asthma patients.5 Therefore, we hypothesize that exposure of AM to HDM/LPS would upregulate genes associated with eosinophil and neutrophil signalling., peer-reviewed

Patients with severe asthma experience severe symptoms and frequent exacerbations despite intensive treatment with inhaled and oral glucocorticoids. Biologics for severe asthma aim to reduce asthma-related and glucocorticoid-induced morbidity. Recently, new biologics targeting interleukin (IL)-5, IL-5 receptor and IL-4/IL-13, which are all cytokines involved in so-called type 2 airway inflammation, were approved for severe asthma. They show a reduction in exacerbation rate and an oral glucocorticoid-sparing effect. Studies with upstream biologics targeting alarmin cytokines such as thymic stromal lymphopoietin (TSLP) and IL-33 are underway, and newly designed bispecific antibodies targeting more than one pathway are in early phases of development. Such pathway-targeted add-on treatments will soon become standard of care for all patients with severe asthma.

Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.1 Disruption and subsequent dysregulation of gut microbiota-related immunologic processes have also been linked to disease severity and response to treatment.2.

ZnO and SnO2 thin films were deposited on glass and Polyetherimide (PEI) flexible substrates by spray pyrolysis deposition at low temperature (250 °C). The structural characterization by X-ray diffraction (XRD) reveals that PEI promotes the crystallization of ZnO and SnO2 thin films while the films deposited on glass substrate are amorphous. The physical investigations show that ZnO/PEI and SnO2/PEI have a good crystalline quality and high transparency in visible range (T>80%). Their gap energies are calculated from absorbance data (3.3 eV for ZnO and 3.72 eV for SnO2). Furthermore, the surface properties are investigated by atomic force microscopy and contact angle measurements. It is found that the ZnO/PEI film has a higher surface roughness (RMS = 20.20 nm ± 0.62 nm) compared to SnO2/PEI (RMS = 5.41 nm ± 0.16 nm). The metal oxides (ZnO and SnO2) catalysts exhibit excellent photodegradation activities under UV irradiation up to 80%. The highest activity was observed for ZnO thin films because it exhibits smaller gap energy. Furthermore, both samples show excellent photocatalytic stability.

Introduction: The complexity and heterogeneous nature of asthma and chronic obstructive pulmonary disease (COPD) results in difficulties in diagnosing and treating patients. Biomarkers that can identify underlying mechanisms, identify patient phenotypes and to predict treatment response could be of great value for adequate treatment. Areas covered: Biomarkers play an important role for the development of novel targeted therapies in airways disease. Blood biomarkers are relatively non-invasive, easy to obtain and easy to apply in routine care. Several blood biomarkers are being used to diagnose and monitor chronic airways diseases, as well as to predict response to treatment and long-term prognosis. Blood eosinophils are the best studied biomarker, the most applied in clinical practice, and until now the most promising of all blood biomarkers. Other blood biomarkers, including serum periostin, IgE and ECP and plasma fibrinogen are less studied and less relevant in clinical practice. Recent developments include the use of antibody assays of many different cytokines at the same time, and ‘omics’ techniques and systems medicine. Expert commentary: With the exception of blood eosinophils, the use of blood biomarkers in asthma and COPD has been rather disappointing. Future research using new technologies like big-data analysis of blood samples from real-life patient cohorts will probably gain better insight into underlying mechanisms of different disease phenotypes. Identification of specific molecular pathways and associated biomarkers will then allow the development of new targets for precision medicine.

A successful deposition of undoped and Fluorine doped tin oxide (TO and FTO) nano films at relatively low temperature 250 °C on flexible substrate (Polyethyerimide) was obtained using the spray pyrolysis technique. The Fluorine doping effects on the structural, morphological and optical properties were investigated. XRD measurements permit textural characterization, and show that the films have a tetragonal polycrystalline structure. The increase of crystalline size and reduction of defects and strain with Fluorine doping improve the crystalline quality. This is may be due to the substitution of O −2 by F - . Furthermore, the structural changes of the films affected the surface roughness which became rough with the Fluorine. This was confirmed by wettability measurements. Moreover, the gap energy exhibits a slight red-shift with F-doping. The photoluminescence spectra showed that Fluorine doping increased the radiative centers, which is confirmed by structural results. The photocatalytic performance of TO and FTO nanofilms were investigated by degradation of crystal violet dye under UV radiations. Results showed that TO and FTO exhibit high photocatalytic activities, which can be enhanced by H 2 O 2 addition.

Introduction: Chronic inflammatory diseases predispose for development of a first pulmonary embolism ( PE). Previous studies showed that corticosteroids, which are the mainstay of treatment for inflammatory diseases, enhance the risk of a first venous thromboembolism. Yet, it is unknown whether corticosteroids also predispose for recurrent events. Therefore, we investigated the association between oral and/or inhaled corticosteroid use and the risk of recurrent PE.Methods: We performed a nested case-control study using the PHARMO Database. Adult patients who had suffered from a first PE for which vitamin K antagonists were prescribed, were eligible. Of these, 384 patients with recurrent PE were matched to 1030 patients without recurrent PE.Results: We showed that oral or inhaled corticosteroids was ever used by 22.7% and 20.6% of patients with recurrent PE, and 23.5% and 21.5% of the patients without recurrent PE. There was an overall association between oral corticosteroid use and the risk of recurrent PE (p = 0.02). Current use of oral corticosteroids increased the risk of recurrent PE (OR 3.74; 95% CI 2.04-6.87), whereas past use reduced the risk (OR 0.46; 95% CI 0.28-0.74). A similar pattern was observed for inhaled corticosteroids, although less strong (p - 0.10).Conclusions: Current use of oral corticosteroids is associated with increased risk of recurrent PE. Whether this increased risk is caused by oral corticosteroids themselves, or by the underlying disease, or both, needs further investigation. Nevertheless, given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk. (C) 2016 Elsevier Ltd. All rights reserved.

Mg-promotion of natural clay based Ni-catalysts was considered, as a way of boosting the dry reforming of methane (DRM) activity of these materials. The results of the DRM experiments performed at temperatures from 600 °C to 850 °C evidenced much higher methane and CO

Transit passengers’ response to crowded conditions has been studied empirically, yet is limitedly included in transport models currently used in the design of policy and infrastructure investments. This has consequences for the practical applicability of these models in studies on, for instance, timetabling, train capacity management strategies, project appraisal, and passenger satisfaction. Here we propose four methods to include the effect of crowding, based on existing studies on passengers’ perception and response as well as often-used crowding indicators. These four alternative methods are implemented in the train passenger assignment procedure of the Dutch national transport model, and evaluated with respect to their impacts on the model results for the Dutch railway network. The four methods relate to four different ways in which an additive trip penalty and/or time-multiplier can be incorporated in the train utility function for different travel purposes, to capture the disutility of crowding as measured by the load factor. The analyses of the test case favor the hybrid method using both a boarding penalty (capturing seat availability upon boarding) and a time-multiplier (capturing physical comfort and safety throughout the trip). This method produces consistent results, while the additional computational effort that it imposes is acceptable. Further empirical underpinning is needed to conclusively show which of these methods best captures passengers’ response behavior quantitatively (for different travel purposes and conditions).

In 2014, we were proud to launch the European Respiratory Society (ERS)/European Lung Foundation (ELF) campaign: Healthy Lungs for Life (HLfL; www.healthylungsforlife.org); a lung health campaign to educate all stakeholders about the importance of prevention and management of lung disease and how this can be achieved. Our inaugural theme, “Breathe Clean Air”, was a timely and impactful topic to kick off with and resonated across the globe with politicians in the EU, journalists in a range of countries, scientists carrying out research with funding from HLfL, the people of Munich who had their lungs tested while the ERS International Congress took place, and those who attended events held by our collaborators across the globe, from India to the USA to New Zealand., ERS/ELF say “take the active option” for Healthy Lungs for Life http://ow.ly/R1WaX

Summary Background Anxiety and depression are prevalent in patients with asthma, and associated with more exacerbations and increased health care utilization. Since psychiatric intervention might improve asthma control, we examined whether patients with severe, prednisone-dependent asthma are at higher risk of these disorders than patients with severe non-prednisone dependent asthma or mild-moderate asthma, and whether they exhibit different personality traits. Methods Sixty-seven adults with severe prednisone-dependent asthma, 47 with severe non-prednisone dependent and 73 patients with mild-moderate asthma completed the HADS depression and anxiety subscale and the NEO-FFI for personality traits. In addition, asthma duration, body mass index and FEV 1 were measured. Results The prevalence of clinically significant depressive symptoms (9% vs. 0 vs. 0%; p = 0.009) and anxiety symptoms (19% vs. 6.4 vs. 5.5%; p = 0.01), was higher in patients with severe, prednisone-dependent asthma than in patients with severe non-prednisone dependent or mild-moderate asthma. Patients with prednisone-dependent asthma were respectively 3.4 (95%CI: 1.0–10.8 p = 0.04) and 3.5 (95%CI: 1.3–9.6 p = 0.01) times more likely to have significant depression symptoms and 1.6 (95%CI: 0.7–3.7, p = 0.2) and 2.5 (95%CI: 01.1–5.5, p = 0.02) times more likely to have symptoms of anxiety than patients with severe non-prednisone dependent or mild-moderate asthma. There were no differences found in personality traits between the 3 groups. Conclusion Patients with severe, prednisone-dependent asthma have more often psychological distress as compared to patients with severe non-prednisone dependent or mild-moderate asthma.

BACKGROUND: Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma. METHODS: In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, we compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of reduction in the glucocorticoid dose (90 to 100% reduction, 75 to less than 90% reduction, 50 to less than 75% reduction, more than 0 to less than 50% reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control during weeks 20 to 24, or withdrawal from treatment). Other outcomes included the rate of asthma exacerbations, asthma control, and safety. RESULTS: The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group (95% confidence interval, 1.25 to 4.56; P=0.008). The median percentage reduction from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as compared with no reduction in the placebo group (P=0.007). Despite receiving a reduced glucocorticoid dose, patients in the mepolizumab group, as compared with those in the placebo group, had a relative reduction of 32% in the annualized rate of exacerbations (1.44 vs. 2.12, P=0.04) and a reduction of 0.52 points with respect to asthma symptoms (P=0.004), as measured on the Asthma Control Questionnaire 5 (in which the minimal clinically important difference is 0.5 points). The safety profile of mepolizumab was similar to that of placebo. CONCLUSIONS: In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. (Funded by GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.).

Asthma is a chronic airway disease characterized by paroxysmal airflow obstruction evoked by irritative stimuli on a background of allergic lung inflammation. Currently, there is no cure for asthma, only symptomatic treatment. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and platelets in the pathophysiology of asthma has increased considerably. Asthma is associated with a procoagulant state in the bronchoalveolar space, further aggravated by impaired local activities of the anticoagulant protein C system and fibrinolysis. Protease-activated receptors have been implicated as the molecular link between coagulation and allergic inflammation in asthma. This review summarizes current knowledge of the impact of the disturbed hemostatic balance in the lungs on asthma severity and manifestations and identifies new possible targets for asthma treatment.

The paper presents the shear frame test with a new method of gripping the fabric sample to describe the shear behaviour of fabrics used in the garment industry under high shear strain conditions (maximum shear angles of 20°). This shear frame test was also used to compare between hysteresis curves given by the Kawabata evaluation system (KES) test, the bias extension test and the shear frame test for 10 woven fabrics. The linear viscoelastic theory was used to analyse the shear relaxation behaviour of the woven fabrics. In addition, in this study, the kernel function of the generalised Maxwell model has been used to describe the viscoelastic properties of the fabrics.

Fabric’s tendency to wrinkle is crucially important to the textile industry as it impacts on the visual appeal of apparels. Current methods of grading this characteristic are very subjective and inadequate. As such, a quantitative method for assessing fabric wrinkling is of the utmost importance for the textile community. To that end, this paper reports on a numerical study of the wrinkling behaviour of cotton‐ and polyester‐woven fabrics using the cylindre creux test. A fabric trellis shear test method was used in order to describe the viscoelastic behaviour of fabrics. Afterwards, an approach by means of continuous mechanics theory is suggested for numerical simulation of the wrinkle recovery of textile‐woven fabric. The numerical procedure used an explicit dynamic scheme for the quasi‐static problem involving complex nonlinear effects (complex contact conditions). To characterise these coined numeric wrinkles, a state analysis of the normal vectors to the fabric surface was considered.

Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. The disease is classified into eight groups. Among them, XP group A (XP-A) is characterized by the presence of neurological abnormalities in addition to cutaneous symptoms. In the present study, we report a particular family with XP-A in which some members showed an atypical clinical presentation, i.e. unexplained neurological abnormalities with discrete skin manifestations. Molecular investigation allowed identification of a novel XPA mutation and complete phenotype-genotype correlation for this new phenotypic expression of XP-A.

Rationale The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. Objectives To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. Methods From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24. Measurements and main results No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups. Conclusions Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).

Rationale Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). Objectives: We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. Methods: Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6+/-9.3 years; FEV1, 1.72+/-0.69 L), 20 patients with asthma (age, 35.4+/-15.1 years; FEV1, 3.32+/-0.86 L), 20 nonsmoking control subjects (age, 56.7+/-9.3 years; FEV1, 3.44+/-0.76 L), and 20 smoking control subjects (age, 56.1+/-5.9 years; FEV1, 3.58+/-0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. Measurements and Main Results: Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P

Background: Asthma and obesity are associated disorders, but the contribution of obesity to difficult-to-treat asthma as well as the mechanisms responsible for this relationship are unclear. The aim of this study was to investigate the relationship between obesity (body mass index ≥ 30) and factors related with asthma severity in patients with difficult-to-treat asthma. Methods: One hundred and thirty-six nonsmoking asthmatic adults with persistent symptoms despite high doses of inhaled or oral corticosteroids and long-acting bronchodilators were studied [70% female, median (range) age 44.6 (18–75) years, 32% on daily oral corticosteroids]. The association between obesity, lung function parameters [forced expiratory volume in 1 s (FEV1), functional residual capacity/total lung capacity (FRC/TLC)], inflammatory markers [blood eosinophils, sputum eosinophils and neutrophils, exhaled nitric oxide (FENO), airway hyperresponsiveness, C-reactive protein (CRP)] and aggravating co-morbid factors (severe chronic sinus disease, gastro-esophageal reflux, recurrent respiratory infections, psychopathology and obstructive sleep apnea) was investigated. Results: Obese patients (n = 29) had a higher FEV1%pred (P = 0.05) and a lower FRC/TLC%pred (P

The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.

Summary Background Persistent airflow limitation is common among patients with severe asthma, but its pathogenesis has not been fully clarified. Severe alpha-1-antitrypsin (AAT) deficiency is a risk factor of chronic airflow limitation and emphysema, and partially deficient phenotypes have been associated with an accelerated decline in lung function. We hypothesized that partial deficiency of AAT (non-PiM AAT phenotype) is a risk factor of persistent airflow limitation in asthma. Methods In 122 patients with severe asthma (86 females; age (median (range)): 44.0yr (18–75)) postbronchodilator FEV 1 and FEV 1 /VC were measured and the AAT phenotype was determined. Persistent airflow limitation was defined as postbronchodilator FEV 1 or FEV 1 /VC 75% pred. Results Six patients (4.9%) had a non-PiM phenotype (1 MF, 3 MS, 1 MZ and 1 SZ). Of the 58 patients with persistent airflow limitation only 1 patient (1.7%) had a non-PiM phenotype vs. 7.8% among the patients without persistent airflow limitation ( P = 0.21 ). Postbronchodilator FEV 1 /VC (% pred.) was higher in the non-PiM patients than in the PiM patients ( P = 0.02 ), the other lung function parameters were not different. Linear regression analysis showed no association between AAT phenotype and FEV 1 % predicted ( P = 0.26 ). Conclusions AAT heterozygoty does not seem to be an important risk factor of persistent airflow limitation in patients with asthma. Although confirmation by longitudinal follow-up studies with larger sample sizes is needed, these results suggest that routine assessment of the AAT phenotype is not indicated in asthmatic patients even if they exhibit fixed airflow limitation.

Severe refractory asthma is a heterogeneous condition with different patterns of severity and different reasons for loss of asthma control. The three main patterns include asthma with frequent exacerbations, asthma with irreversible airway obstruction, and asthma with reduced sensitivity or resistance to corticosteroids. Each of these patterns has distinct risk factors. The assessment of patients with severe asthma requires a systematic, diagnostic and management protocol. The majority of patients will benefit from thorough analysis and treatment of aggravating factors. In some patients with severe refractory asthma, in particular those with concomitant chronic rhinosinusitis, long-term administration of systemic corticosteroids may be necessary. In these patients all efforts should be directed towards reducing the dose of corticosteroids as much as possible. Although several corticosteroid-sparing agents and immunosuppressants have been proposed in the literature, none of these has gained complete acceptance in clinical practice, either because of limited efficacy or unacceptable adverse effects. Novel potent anti-inflammatory therapies aimed at reducing the need for systemic corticosteroids in patients with severe, refractory asthma are urgently needed.

Background: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease. Objective: This study sought to determine the remission rate and identify predictors of persistence and remission of adult-onset asthma. Methods: Two hundred adult patients with recently diagnosed ( = 1 year and no asthma medication use for >= 1 year. Descriptive statistics and logistic regression analysis were performed. Results: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps, and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these 2 characteristics had

In this contribution, an inverse identification strategy of constitutive laws for elastoplastic behaviour is presented. The proposed inverse algorithm is composed on an appropriate finite element calculation combined with an optimisation procedure. It is applied to identify material anisotropic coefficients using a set up of easy performed laboratory tests. The used experimental data are the plane tensile test and the off axes tensile tests. The identified behaviour models are mainly based on Hill's quadratic yield criterion. Two cases of this yield criterion have been considered: the transverse isotropic and the orthotropic one under an associated and non-associated flow rule assumptions for each case. The yield surface has been assumed to expand isotropically (isotropic strain hardening law) as a function of the plastic work. In order to better describe anisotropic plastic properties of the studied materials, a recently planar anisotropic yield function is used. It is a non-quadratic yield criterion which takes account of anisotropic yield stresses as well as anisotropic strain ratios. It is subsequently shown that the agreement between inverse identification results and experimental measurements were improved. We prove also that the presented strategy is a good alternative to the simplified homogeneous tests assumption, especially for the plane tensile test.