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.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

First Measurement of Collectivity of Coexisting Shapes Based on Type II Shell Evolution: The Case of

BACKGROUND: Type II shell evolution has recently been identified as a microscopic cause for nuclear shape coexistence. PURPOSE: Establish a low-lying rotational band in ^{96}Zr. METHODS: High-resolution inelastic electron scattering and a relative analysis of transition strengths are used. RESULTS: The B(E2;0_{1}^{+}→2_{2}^{+}) value is measured and electromagnetic decay strengths of the 2_{2}^{+} state are deduced. CONCLUSIONS: Shape coexistence is established for ^{96}Zr. Type II shell evolution provides a systematic and quantitative mechanism to understand deformation at low excitation energies.

Effects of omalizumab in severe asthmatics across ages: A real life Italian experience.

BACKGROUND: This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18-39, 40-64 and ≥ 65 years. RESULTS: Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased significantly after Omalizumab but the percentage of exacerbation-free patients was higher in younger people (76.9%) compared to middle aged patients (49.2%) and the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826], p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to elderly asthmatics. Also, a significantly reduced ACT improvement (ß = -1.070; p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab improves all asthma outcomes independently of age, although the magnitude of the effects observed in the elderly seems to be lower than in the other age groups.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and sociocultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

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.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and socio-cultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

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.

Spirometric criteria to diagnose airway obstruction in the elderly: fixed ratio vs lower limit of normal.

COPD is the most common chronic lung disease. It becomes more prevalent with increasing age but remains under-diagnosed in the elderly. A heated debate concerns the most suitable way to diagnose airway obstruction in this age group. Most COPD guidelines recommend to use a FEV1/FVC of 0.70 as threshold to define an obstructive ventilatory defect. While the use of a 0.70 ratio may be simple, it may result in under-diagnosis of airflow obstruction in young people and over-diagnosis in the elderly due to an age-related decline in pulmonary volumes, especially in FEV1. This might lead to unnecessary use of medications and increased risk of adverse effects. A proposed strategy for reducing the misclassification of airway obstruction include the use of the statistically derived lower limit of normal (LLN) for FEV1/FVC, calculated as the fifth percentile of the normal distribution in a healthy population. Some authors addressed the possibility to evaluate lung function through high-resolution CT. In contrast to spirometry, CT imaging may allow for regional assessment of the compartments involved (airways, parenchyma, vasculature), and may enable a phenotype-driven characterization of COPD. Bhatt et al. recently observed that a small proportion (7%) of subjects with CT-defined emphysema were identified by the 0.70 threshold for FEV1/FVC but not by the LLN. However, there is no evidence that CT-emphysema corresponds to a clinical entity that can benefit by inhaled therapy. Further studies are needed to assess the classificatory and prognostic value of the different proposed criteria to diagnose airway obstruction in the elderly.

Generation of a monoclonal antibody against the myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) suitable for biochemical and for immunohistochemical investigations of CNP.

The functional role of CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase), a minor component of central and peripheral myelin is still unclear. Here we describe preparation of a monoclonal antibody directed against CNP. The antibody, of the immunoglobulin IgG1 type, raised with a basic 46 kDa membrane-associated protein solubilized from pig cerebellar membranes, can be used to detect immunoreactivity in solubilized brain homogenates from pig, mouse, rat, sheep, cow and man, in cerebrum and cerebellum, but not in other tissues such as liver, skeletal and heart muscle. The antibody recognizes the CNP doublet band and shows no cross-reactivity with any of the other brain proteins solubilized. In tissue sections from paraformaldehyde-fixed rat brain the antigen was localized in oligodendrocytes. In cultured glial cells from newborn mice the antibody stained cells which were identified as oligodendrocytes by co-localization of myelin basic protein. Even cells from a C6 rat glioma cell line, which contain very little of CNP, were labeled by the monoclonal antibody. Thus the monoclonal antibody recognizing CNP from several species is suitable for immunocytochemical investigations and also for biochemical studies of CNP, since the antibody has been employed for immunoprecipitation and immunopurification of CNP in crude brain homogenates.

Anti-epidermal growth factor receptor monoclonal antibodies affecting signal transduction.

Monoclonal antibodies prepared against tyrosine phosphorylated epidermal growth factor receptor (EGFR) were tested for their effects on transmembrane signal transduction in A431 tumor cells. Monoclonal antibodies (mab) defined by SDS-sensitive epitopes, i.e., epitopes with conformational specificity, were most effective. Mab 5-125 reacting with a site of the extracellular EGFR domain blocked EGF-binding and cell proliferation in vitro, as well as tumor growth in vivo. However, this mab appeared not to be internalized upon binding to EGFR and did not trigger EGFR autophosphorylation. In contrast, mab 5-D43, also defined by an SDS-sensitive epitope and reacting with an extracellular EGFR site, did not block EGF binding but was readily internalized after binding to EGFR of untreated A431 cells. This mab induced EGFR tyrosine phosphorylation in cell lysates and tyrosine-specific autophosphorylation of insolubilized EGFR immune complexes. Cell growth in vitro was greatly stimulated in the presence of mab 5-D43. Since interaction of mab 5-D43 with EGFR induced most EGF-specific functions, although it did not bind to the EGF-specific site of EGFR, we have to assume that binding of mab 5-D43 to EGFR induced a conformational shift that activated the cytoplasmic EGFR kinase site. On the other hand, activation and/or accessibility of the EGFR kinase site could be blocked by mab 1-594, which is defined by an SDS-insensitive protein epitope of the cytoplasmic EGFR domain. Blocking of the EGFR kinase site by mab 1-594 also abolished EGF-induced tyrosine phosphorylation of endogenous cellular substrates with molecular masses of 145, 97, 85, 37, and 32 kDa, as well as of exogenous substrates such as GAT copolymer.

Highly specific characterization of tyrosine phosphoproteins in tumor cells based on monoclonal antibodies defined by conjugated phosphotyramine.

Phosphotyrosine proteins of four different tumor cell lines were characterized by monoclonal antibodies exhibiting high affinity binding to phosphotyrosine. For the preparation of the antibody-producing mouse hybridoma cell lines we used a novel kind of immunizing antigen with phosphotyramine conjugated directly to carboxylic groups of carrier proteins. Screening for high affinity binding antibodies was based on their selective reactivity in immunoprecipitation, affinity chromatography and immunofluorescence. By means of affinity chromatography we established a one-step purification of phosphotyrosine proteins yielding substantial quantities of highly pure 170kDa EGF receptor from A431 tumor cells, 210kDa bcr-abl gene product from K562 tumor cells and 120 kDa transforming protein of the Abelson murine leukemia virus from TK tumor cells. Cross-reactivity with phosphoproteins containing no phosphotyrosine was not observed.