The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. RESULTS: Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. CONCLUSIONS: In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Is mild asthma in real life always in the Green Zone?

Asthma is a chronic inflammatory disease of the airways that is characterized by variable narrowing of the airways and symptoms of intermittent dyspnea, wheezing, and nighttime or early-morning coughing. Asthma is a major health problem throughout the world, affecting an estimated 315 million persons of all ages. Asthma is clinically heterogeneous, and its pathophysiology is complex. For convenience, asthma action plans are often broken down into three zones, usually based on peak flow meter recordings: green, yellow, and red according to the level of lung function impairment. Recent evidence shows that every asthmatic is potentially at risk for severe exacerbation independently of his/her zone, including the green zone. Furthermore, in real life scenario asthmatic patients can have poor perception of their symptoms or/and overestimate their level of asthma control, and this can obviously confound the clinical picture and favor sudden worsening of symptoms. To understand how to treat these patients, as well as how to assess their future risk, can make a difference in terms of clinical outcomes and prognosis. Following the suggestions and concerns recently published, who recently focused on the clinical management of mild asthma, we aimed at exploring strengthens and gaps in the daily management of the mildest forms of the disease, with a focus on alternative diagnostic and therapeutic strategies in approaching the "green" patient in clinical practice.

Bronchial thermoplasty in severe asthma: food for thoughts.

Asthma is a complex inflammatory disorder of the airways characterized by airway hyper-responsiveness and variable, reversible, airflow obstruction. Bronchial thermoplasty (BT) is a new modality for treating asthma. It targets airway smooth muscles (ASM) by delivering a controlled specific amount of thermal energy (radiofrequency ablation) to the airway wall through a dedicated catheter. The use of bronchial thermoplasty has been widely discussed for its potential in the treatment of asthma, since it seems to be able to reduce the symptoms of asthma. The definitive study for BT (AIR2 trial) employed a randomized, double-blind, sham-controlled design and enrolled 288 subjects with severe persistent asthma from 30 US and international centers. The results of the AIR2 trial demonstrated clinically significant benefits of BT compared with the sham group at one year post-treatment, including an improvement in asthma-related quality of life, 32% reduction in severe exacerbations, 84% reduction in emergency department visits for asthma symptoms, and a 66% reduction in time lost from work/school/other daily activities because of asthma symptoms. Preclinical work showed that ASM is reduced after BT by at least 3 years after treatment. The recent article from the ARI2 trial study group analyses the long-term safety and effectiveness of BT in patients with severe persistent asthma and demonstrates the 5-year durability of the benefits of BT in the control of symptoms and safety. It supports the evidence that reduction in asthma attacks, ER visits, and hospitalizations for respiratory symptoms are maintained for at least 5 years. There is a pressing need to understand the underlying mechanism(s) of BT and how the delivered heat is translated into clinical benefit. This necessitates additional investigation to identify disease and patient characteristics that would enable accurate phenotyping of positive responders to avoid unnecessary procedures and risks.

The adhesion molecule ICAM-1 is overexpressed in patients with Hymenoptera venom allergy and decreases after ultrarush venom immunotherapy.

Adhesion molecules, including ICAM-1, are an important factor in allergic inflammation caused by inhalant allergens, but there are no studies investigating their possible role in Hymenoptera venom allergy (HVA). We measured the level of ICAM-1 in 13 venom-allergic patients before and after ultra-rush venom immunotherapy (VIT). Eight patients were treated by yellow jacket venom and 5 were treated by honeybee venom. Serum ICAM-1 levels were assayed by an immunoenzymatic method, with a detection limit of 0.35 ng/ml. The mean level of ICAM-1 changed from 316.4±78.2 ng/ml before VIT to 294.7±77.9 after VIT. This difference was statistically significant (p = 0.019). These findings show that in patients with HVA there is an over-expression of ICAM-1, and that ultra-rush VIT significantly decreases ICAM-1 levels. It is likely that the known ability of VIT to correct the imbalance in T lymphocytes subpopulations and in the associated production of cytokines may account for this observation. In fact, such cytokines include IL-4 and TNF-alpha, that up-regulate adhesion molecules.

A meta-analysis of open versus arthroscopic Bankart repair using suture anchors.

Purpose of this study is to conduct a meta-analysis comparing the results of open and arthroscopic Bankart repair using suture anchors in recurrent traumatic anterior shoulder instability. Using Medline Pubmed, Cochrane and Embase databases we performed a search of all published articles. We included only studies that compared open and arthroscopic repair using suture anchors. Statistical analysis was performed using chi-square test. Six studies met the inclusion criteria. The total number of patients was 501, 234 suture anchors and 267 open. The rate of recurrent instability in the arthroscopic group was 6% versus 6.7% in the open group; rate of reoperation was 4.7% in the arthroscopic group vs. 6.6% in open (difference not statistically significant). The difference was statistically significant only in the studies after 2002 (2.9% of recurrence in the arthroscopic group vs. 9.2% in open; 2.2% of reoperation in the arthroscopic group vs. 9.2% in open). Results regarding function couldn't be combined because of non-homogeneous scores reported in the original articles, but the arthroscopic treatment led to better functional results. Arthroscopic repair using suture anchors results in similar redislocation and reoperation rate compared to open Bankart repair; however, we need larger and more homogeneous prospective studies to confirm these findings.

Extracorporeal shock waves increase interleukin-10 expression by human osteoarthritic and healthy osteoblasts in vitro.

OBJECTIVE: Extra corporeal shock waves (ESW) have been proposed as additional therapy in bone fracture repair and osteoarthrtitis (OA). However, little is known on the effects of ESW on osteoblast metabolism. The aim of this study was to evaluate phenotype changes of healthy and OA human osteoblasts following ESW treatment. METHODS: Osteoblasts were isolated from subchondral bone of 13 OA patients and 7 healthy donors. Osteoblasts were treated or not with ESW at different levels of energy and impulses. IL-10, TNF-alpha, CD29/Beta1 integrin, and CD105/endoglin expression was evaluated by flowcytometry. RESULTS: Intracellular IL-10 significantly increased using 1000 impulses at 0.055 mJ/mm2 in both healthy and OA osteoblasts in comparison with untreated osteoblasts (p<0.01). Only in the OA osteoblasts CD29 and CD105 expression significantly increased at 500 impulses and 0.17 mJ/mm2 ESW treatment (p<0.05). CONCLUSION: ESW are capable of modifying IL-10 expression in osteoblasts. There is evidence that IL-10 can play a role in bone remodelling by inhibiting osteoclast differentiation and this suggests that ESW may favour bone growth and healing. This further supports the use of ESW in treating bone fracture to promote callus formation. However, the possible use of ESW in OA therapy needs further studies since in OA, osteoblast metabolism is already enhanced with bone sclerosis and ESW application may further increase bone deposition and osteophyte formation, leading to a subsequent worsening of the disease.

Public Prevention Plans to Manage Climate Change and Respiratory Allergic Diseases. Innovative Models Used in Campania Region (Italy): The Twinning Aria Implementation and the Allergy Safe Tree Decalogue.

In recent years, climate change has been influenced by air pollution, and this destructive combination has justifiably sounded an alarm for nations and many institutional bodies worldwide. Official reports state that the emission of greenhouse gases produced by human activity are growing, and consequently also the average temperature. The World Health Organization (WHO) believes that health effects expected in the future due to climate change will be dramatic, and has invited international groups to investigate potential remedies. A task force has been established by the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC), with the aim to actively work on correlation between pollution and climate change. The Task Force provided prevention tools to suggest city leaders how to improve the health conditions of allergic people in public urban parks. The "Allergy Safe Tree Decalogue" suggests the preparation and maintenance of public low allergy-impact greenery. Through the Twinning ARIA project, the Division for the Promotion and Enhancement of Health Innovation Programs of Campania Region (Italy), sought to promote the implementation of the project in the regional Health System. The main objective will be to investigate the current use and usefulness of mobile phone Apps in the management of allergic respiratory disease, through Mobile Airways Sentinel networK (MASK), the Phase 3 of the ARIA initiative, based on the freely available MASK App (the Allergy Diary, Android and iOS platforms). The effects of these prevention activities will be registered and compared with monitoring efforts thanks to the Aerobiology Units, located throughout the Campania area. A joint effort between researchers and public administrations for the implementation of prevention plans coherently with the two models proposed in a specific area, i.e. the Decalogue for public administrations and the MASK Allergy Diary app for individual patients suffering from allergy, will be implemented as a pilot.

Allergy and the cardiovascular system.

The most dangerous and life-threatening manifestation of allergic diseases is anaphylaxis, a condition in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. The heart is both a source and a target of chemical mediators released during allergic reactions. Mast cells are abundant in the human heart, where they are located predominantly around the adventitia of large coronary arteries and in close contact with the small intramural vessels. Cardiac mast cells can be activated by a variety of stimuli including allergens, complement factors, general anesthetics and muscle relaxants. Mediators released from immunologically activated human heart mast cells strongly influence ventricular function, cardiac rhythm and coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating factor (PAF) exert negative inotropic effects and induce myocardial depression that contribute significantly to the pathogenesis of anaphylactic shock. Moreover, cardiac mast cells release chymase and renin that activates the angiotensin system locally, which further induces arteriolar vasoconstriction. The number and density of cardiac mast cells is increased in patients with ischaemic heart disease and dilated cardiomyopathies. This observation may help explain why these conditions are major risk factors for fatal anaphylaxis. A better understanding of the mechanisms involved in cardiac mast cell activation may lead to an improvement in prevention and treatment of systemic anaphylaxis.

[Functional analysis after Achilles tendon repair]. / Analisi funzionale dopo tenorraffia dell'Achille.

The Achilles tendon rupture (ATR) is a severe injury and requires a surgical treatment which can result in functional impairment, limiting unprofessional sports activities. In order to evaluate this potential impairment 20 subjects (SG) who had received surgical treatment for ATR and 20 healthy subjects (CG) were required to execute vertical jump according to counter movement jump and squat jump protocol. For both groups the flying time (Tv) of each foot has been acquired, adopting accelerometric transducers positioned posteriorly at the level of malleolar axis. The SG's Tv is significantly lesser than the CG's one, demonstrating an inferior global performance respect to healthy people and the operated leg has a Tv 6% higher than the contralateral, while in the CG there are no statistical difference between the Tv of the limbs. For seven operated subjects Tv values are lesser than threshold values obtained from CG. For them sports activity which implies high and cyclic stress on the lower limbs could be dangerous. Functional evaluation, consequently, allow to assess impairments not differently estimable.

[Manual lymph drainage of post-mastectomy "big arm"]. / Linfodrenaggio manuale nel "braccio grosso" post-mastectomia.

We estimate the effectiveness of the manual lymphodrainage in the patients with post-mastectomy lymphedema of the upper limb associated to axillary lymphnodes dissection of the ipsilateral arm. The best results were found in the patients with soft and recent lymphedema (which means that was seen within one year); the worst were found in the chronic hard lymphedema. An important psychological assistance and physiotherapy were required to complete the rehabilitation. However, the physiotherapy was very effective when associated to pressed bandage of the arm, at the end of the LDM therapy. Furthermore, the muscle contraction in the bandage had reinforced the lymphoematic pump effect.

Asthma is associated with increased susceptibility to infection.

Asthma is a chronic inflammatory disorder of the airways characterized by airway hyperresponsiveness and airflow limitation. Despite respiratory symptoms may be episodic, progressive changes occur in the structure of the airway, leading to its irreversible remodeling. Changes include mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, sub-basement membrane fibrosis and angiogenesis. The risk factors for developing asthma are a combination of genetic predisposition along with environmental exposure to inhaled substances and particles that may provoke allergic reactions or irritate the airways, such as in- and out-door allergens, tobacco smoke, chemical irritants in the workplace and air pollution. Asthma is a clinically heterogeneous entity due to the complexity of its pathogenetic substrate. Recent evidence suggests asthma to be associated with a sort of immunodeficiency accounting for an increased susceptibility to infection in asthmatic patients. The role of infections as triggers and promoters of disease progression is well established. Conversely, the impact of asthma as a predisposing condition to infection has not clearly been addressed. Such a topic will be the focus of the present review.

Asymmetric dimethylarginine (ADMA): will be or will not be a new revolutionary biomarker of bronchial asthma?

Carraro et al. measured asymmetric dimethylarginine (ADMA) in the exhaled breath condensate (EBC) obtained from children with asthma and from healthy subjects. The authors demonstrated higher levels of ADMA in EBC of asthmatics compared to controls. ADMA levels in EBC did not correlate with serum levels, lung function parameters, and fractional exhaled nitric oxide. ADMA levels in EBC did not significantly differ between asthmatic patients regularly treated with inhaled steroids and those who were steroid naïve. Further studies are necessary in order to evaluate the role of this biomarker in the characterization of phenotypes of severe bronchial asthma.

Bronchoscopy in sarcoidosis: union is strength.

Sarcoidosis is a benign disease of unknown etiology that is characterized by the formation of noncaseating epithelioid cell granulomas. Although a multisystemic disease, it primarily affects the lung and the lymphatic system of the body. When a histological diagnosis is required, bronchoscopy is frequently employed because allows tissue sampling from several anatomic sources, such as airways, lung parenchyma and hilar/mediastinal nodes. Transbronchial lung biopsies (TBLB), endobronchial biopsies (EBB) and conventional transbronchial needle aspiration (cTBNA) have long been the only bronchoscopic techniques to diagnose sarcoid granulomas, until the advent of endobronchial ultrasound guided needle aspiration (EBUS-TBNA). This technique shows excellent yield in sampling mediastinal adenopathies with a higher sensitivity than the conventional technique in sarcoidosis as well. Furthermore, non controlled studies, demonstrated its diagnostic superiority than EBB and TBLB in stages I (hilar adenopathies only) and II (hilar lymph nodes and parenchymal infiltrations) thoracic sarcoidosis. In a recent study, Gupta et al., randomized 130 patients with suspected stage I and II disease to undergo EBUS-TBNA or cTBNA in conjunction with transbronchial and endobronchial biopsies. The Authors demonstrated that the yield of cTBNA added to EBB and TBLB is similar to EBUS-TBNA plus transbronchial biopsies, although ultrasound guided transbronchial needle aspiration shows the best single diagnostic efficacy. In this review article we aimed to discuss the findings by Gupta in the context of medical literature, highlighting the importance of adding nodal aspirations (with or without ultrasound guidance) with bronchial and transbronchial samples to gain the optimal sensitivity in obtaining histological confirmation. We finally pointed out the need for future studies to evaluate the potential role of rapid on-site evaluation (ROSE) of needle aspirates in reducing additional sampling and related costs and complications.

Asymmetric dimethylarginine (ADMA): will be or will not be a new revolutionary biomarker of bronchial asthma.

Carraro et al. measured asymmetric dimethylarginine (ADMA) in the exhaled breath condensate (EBC) obtained from children with asthma and from healthy subjects. The authors demonstrated higher levels of ADMA in EBC of asthmatics compared to controls. ADMA levels in EBC did not correlate with serum levels, lung function parameters, and fractional exhaled nitric oxide. ADMA levels in EBC did not significantly differ between asthmatic patients regularly treated with inhaled steroids and those who were steroid naïve. Further studies are necessary in order to evaluate the role of this biomarker in the characterization of phenotypes of severe bronchial asthma.

Dupilumab-associated conjunctivitis in patients with atopic dermatitis: a multicenter real-life experience

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