Immunoglobulin free light chains in severe asthma patient: Could they be a new biomarker?

BACKGROUND: Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease. METHODS: We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable. RESULTS: FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization. CONCLUSIONS: Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for clinical severity parameters.

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness.

OBJECTIVE: The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of adult patients affected by severe CRSwNP treated with dupilumab. Maxillofacial computed tomography, evaluation of blood eosinophils and serum IgE levels, measurement of nasal polyp score (NPS), smell identification test (SSIT-16), sinonasal outcome test-22 (SNOT-22) and asthma control test (ACT) were performed. Follow-up was conducted at 2 weeks, and at 1, 3, and 6 months. Adverse events and the efficacy of treatment were monitored. RESULTS: 23 patients were enrolled. After 15 days, scores of the SNOT-22, NPS and SSIT-16 significantly improved. These outcomes were also maintained after 1, 3, and 6 months (p < 0.001). At this latter follow-up time, SNOT-22 showed a change of -33.10 (p < 0.001), NPS -3.36 (p < 0.001) and SSIT-16 +5.60 (p < 0.001). In all, 26.1% of patients experienced early minor complications. CONCLUSIONS: In the present study, dupilumab was effective in the treatment of severe uncontrolled CRSwNP, demonstrating a quick significant improvement in both questionnaires and endoscopic evaluation. Only minor complications were observed.

Elasticity assessment of electrospun nanofibrous vascular grafts: a comparison with femoral ovine arteries.

Development of successful small-diameter vascular grafts constitutes a real challenge to biomaterial engineering. In most cases these grafts fail in-vivo due to the presence of a mechanical mismatch between the native vessel and the vascular graft. Biomechanical characterization of real native vessels provides significant information for synthetic graft development. Electrospun nanofibrous vascular grafts emerge as a potential tailor made solution to this problem. PLLA-electrospun nanofibrous tubular structures were prepared and selected as model bioresorbable grafts. An experimental setup, using gold standard and high resolution ultrasound techniques, was adapted to characterize in vitro the poly(L-lactic acid) (PLLA) electrospun structures. The grafts were subjected to near physiologic pulsated pressure conditions, following the pressure-diameter loop approach and the criteria stated in the international standard for cardiovascular implants-tubular vascular prostheses. Additionally, ovine femoral arteries were subjected to a similar evaluation. Measurements of pressure and diameter variations allowed the estimation of dynamical compliance (%C, 10(-2) mmHg) and the pressure-strain elastic modulus (E(Pε), 10(6) dyn cm(-2)) of the abovementioned vessels (grafts and arteries). Nanofibrous PLLA showed a decrease in %C (1.38±0.21, 0.93±0.13 and 0.76±0.15) concomitant to an increase in EPε (10.57±0.97, 14.31±1.47 and 17.63±2.61) corresponding to pressure ranges of 50 to 90 mmHg, 80 to 120 mmHg and 100 to 150 mmHg, respectively. Furthermore, femoral arteries exhibited a decrease in %C (8.52±1.15 and 0.79±0.20) and an increase in E(Pε) (1.66±0.30 and 15.76±4.78) corresponding to pressure ranges of 50-90 mmHg (elastin zone) and 100-130 mmHg (collagen zone). Arterial mechanics framework, extensively applied in our previous works, was successfully used to characterize PLLA vascular grafts in vitro, although its application can be directly extended to in vivo experiences, in conscious and chronically instrumented animals. The specific design and construction of the electrospun nanofibrous PLLA vascular grafts assessed in this work, showed similar mechanical properties as the ones observed in femoral arteries, at the collagen pressure range.

Multiple pulmonary nodules and unexplained fever: when the pulmonologist fails.

We describe herein a difficult case of persistent and refractory fever, associated with multiple lung nodules, progressive respiratory failure and general deterioration. Our patient was carefully investigated for the possible causes of his symptoms, using current and advanced diagnostic procedures, either serological or by imaging. The confirmatory diagnosis of anaplastic T-cell lymphoma, was obtained only after an invasive procedure (with severe pneumothorax), although it was too late. This suggests that also very rare diseases should be considered in the presence of unexplained signs/symptoms, and that in such cases, aggressive diagnostic procedures should be applied as early as possible.

Waterpipe smoking: not necessarily less hazardous than cigarette smoking : Possible consequences for (cardiovascular) disease.

CONTEXT: Cigarette smoking has declined over the last years in modern countries. On the contrary, waterpipe smoking has increased, especially among young people visiting waterpipe bars. Unfortunately, most waterpipe smokers seem to know little about the possible cardiovascular and other health consequences of waterpipe smoking. OBJECTIVE: To describe by narrative literature review the known adverse consequences for the human body caused by smoking the waterpipe compared with the consequences of smoking normal cigarettes. Also, to get a picture of public awareness of these consequences as deducted from the literature and a small new survey in the Netherlands. RESULTS/CONCLUSIONS: Tobacco smoking is associated with serious adverse (cardiovascular) health effects, and there is no evidence that these effects are less serious if a waterpipe is used. The increasing use together with the limited amount of awareness and attention for the possible health consequences of smoking the waterpipe is worrisome. Especially considering the increasing acceptance and use of the waterpipe among the youth. Therefore we recommend more systematic research into the possible health hazards of waterpipe smoking. In the meantime education campaigns and materials are needed to raise public awareness on the possible health risks of waterpipe use.

An hemodynamic work bench for in-vitro measurements in arterial bifurcations: experimental results and comparison with the output of a simplified CFD model.

To quantify fluid-structure interactions in arterial walls, from a biomechanical standpoint, a complete characterization of blood flow, shear stress in the interface between blood and endothelium, wall elasticity and wall stresses distribution are needed.

FEV6 assessment in spirometric abnormalities screening: the first population-based study in Italian pharmacies.

AIM: In recent years, the FEV1/FEV in six seconds ratio has been proposed and validated as a parameter for screening of airways obstruction and restriction. In this context an electronic spirometry screening of pharmacy customers could lead to significant benefits such as improving the appropriateness of diagnostic test prescription and facilitating the early diagnosis of asthma and chronic obstructive pulmonary disease (COPD). METHODS: Customers of 500 pharmacies in the italian Piemonte region were proposed to test their ventilatory function by an electronic spirometer, PiKo-6®, to find out probably obstruction (pO) and probably restriction (pR). All tests have been carried out by purposely trained pharmacists. Moreover, data regarding sampled subjects' gender, age, height, weight, smoke, pharmacology and therapies used were registered. A web application has been created to collect and analyze the data. RESULTS: Male smokers confirmed a percentage of pO similar to the one predicted in obstructive lung disease (OLD) in international literature (7%); higher percentages of pO (8%) and pR (35%) were instead found in underweight people. When the data are broken down into therapeutic categories, the highest number of pO (12%) and pR (38%) was found in patients in therapy with bronchodilators, in diabetic patients (pR 41%), and in people treated with diuretics (pO 7%, pR 46%) CONCLUSION: Data seem to suggest the six-second spirometry as a valid screening tool for the detection of possible airway obstruction and restriction in pharmacies setting. Results point out the possibility of rationalizing the access to medical visits and of optimizing prescriptive appropriateness. The above mentioned points will lead to save public money and will strengthen the role of the Community Pharmacy as health posts of Italian Health National System.

Biomarkers in obstructive respiratory diseases: an update.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, with the involvement of many inflammatory cells and mediators. Traditionally, this inflammation is thought to spread to a systemic level, thus inducing damage of different organs. However, other pathogenetic mechanisms could take part to the above-described process, and some open questions need to be solved. Due to the burden and increasing prevalence of COPD, the opportunity to find biomarkers that can potentially be useful in identifying individuals with the disease, or better, prior to symptoms onset, to diagnose and properly manage the respiratory symptoms, as well as to evaluate the response to treatment and to select specific subtypes of patients for tailored treatments is strongly advocated. Several mediators, enzymes, hormones and cells have been claimed to adhere to this objective. Moreover, the presence of comorbid or concomitant diseases can variably influence the concentration of specific biomarkers in samples of individuals with COPD, and age-related functional and structural changes (inflammaging) can further confuse the biological pattern. Several observations have been performed in the last decades; nevertheless, no biomarker is currently considered as satisfying all the above-mentioned issues. The "Evaluation of COPD longitudinally to identify predictive surrogates and points (ECLIPSE)" study has specifically explored the possibility to identify novel biomarkers that correlate with clinically relevant COPD subtypes and with markers of disease progression. Among the thirty-four biomarkers considered, 15 resulted to be increased in COPD patients rather than in smoker and non-smoker controls. Specific lung proteins such as CC-16 and SPD are promising in detecting lung damage, exacerbation susceptibility or responsiveness to treatment. The ECLIPSE findings confirm that, to date, the use of a single biomarker is not sufficient, but the combination of novel biomarkers with the already existing tools could improve our skills in optimizing treatment of COPD patients.

The excitation functional for magnetic stimulation of fibers.

Threshold problems in electric stimulation of nerve and muscle fibers have been studied from a theoretical standpoint using the excitation functional. Here the excitation functional is extended to magnetic stimulation of excitable nerve and muscle fibers. A unified derivation of the functional is done, for (non myelinated) nerve and muscle fibers, by means of the nonlinear cable equation with a Fitzhugh-Nagumo membrane model and a generalized Rattay's activating function. The identification problem of the excitation functional for magnetic stimulation, from strength-duration experimental data, is briefly considered.

[Hepatitis B virus infection in habitual sexual partners]. / Infezione da virus della epatite B in partners sessuali abituali.

Habitual heterosexual contacts of chronic HBV infection carriers show high prevalence of infection markers that does not result to be sex related, and results significantly associated to increase of age, presumably as a consequence of duration of exposure. Concomitance of habitual sexual contacts does not represent in an infected family setting a risk factor of higher prevalence of HBV infection, in respect of multitude of occurrences of unperceivable expositions to contagion.