Simona Santangelo

Pre-polysomnographic assessment using the Pittsburgh Sleep Quality Index questionnaire is not useful in identifying people at higher risk for obstructive sleep apnea

Background Polysomnography remains the diagnostic gold standard for obstructive sleep apnea syndrome (OSAS), but it is time consuming and requires dedicated personnel and setting. It may be more useful to plan a polysomnogram based on a preliminary screening. Objective To verify whether a questionnaire of general quality of sleep, the Pittsburgh Sleep Quality Index (PSQI), could outperform a dedicated questionnaire (Epworth Sleep Scale: ESS) in targeting OSAS patients in an at risk population. Methods 254 consecutive subjects attending the outpatient clinic for respiratory diseases were clinically evaluated for sleep apnea and referred to a 12 channel night-time polysomnography. All patients were administered the ESS and the PSQI before the procedure. The correlation between the Apnoea/Hypopnoea Index (AHI) and the global score of the PSQI was calculated; Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), Diagnostic accuracy and the area under the receiver operating characteristic curve (AUC) were calculated. ESS performance was used as a control reference. Results The mean age was 65.8 (standard deviation: 12.1) and the study group was 68.4% male. The mean BMI was 38.5; SD 7.7. Prevalence of OSAS in the study population was 55.5%; OSAS was severe in 60.5% of OSAS patients. ESS was significantly, but weakly, correlated with the AHI (AHI vs ESS: R = 0.308; p < 0.001), whereas PSQI was not (R = 0.037; p = 0.581). Both PSQI and ESS, however, performed unsatisfactorily: sensitivity 37.8% and 69.7%; Specificity 76.1% and 31.0%; Diagnostic Accuracy 57.5% and 49.8%; PPV 60% and 48.7%; NPV 56.3% and 52.2%; AUC 0.589 and 0.509, respectively. Conclusions The PSQI score is not helpful in the pre-polysomnographic assessment of people with suspected OSAS. Further studies are required to provide reliable pre-clinical instruments targeting patients amenable to polysomnography.

Genetic background of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive fibrosing interstitial pneumonia. The histological pattern, which displays dense fibrosis with active areas of fibroblastic proliferation, suggests a pathogenetic role of aberrant response to healing of multiple microscopic, repeated alveolar epithelial injuries. Although the exact etiology of the disease is still under investigation, several studies suggest that a combination of genetic and environmental factors may play a causal role. The aim of this review is to describe the genetic background of IPF, reporting the latest advancements made possible by genomic techniques that allow a high-throughput analysis and the identification of target genes implicated in IPF. This information may help to clarify pivotal aspects on prognosis and diagnosis, and may help to identify potential targets for future therapies.

Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches

Alpha-1 antitrypsin (A1AT) is a 52-kDa, acute phase glycoprotein encoded by the protease inhibitor (PI) locus, located on the long arm of chromosome 14 (14q31-32.3). Its structure is composed of a total of 7 exons, 4 coding (II, III, IV, and V) and 3 non-coding (IA, IB, and IC). A1AT is produced primarily by hepatocytes and acts as a serine protease inhibitor with antiprotease and immunoregulatory activities. The main target of A1AT is neutrophil elastase (NE), an enzyme released during a neutrophil-mediated inflammatory process. When the enzyme is not adequately balanced by A1AT activity, it can cause tissue injury and destruction. A1AT deficiency (A1ATD) is a genetic autosomal recessive disease, characterized by low serum levels of A1AT. The condition may lead to liver disease, early-onset pulmonary emphysema and, rare multi-organ vasculitis, necrotizing panniculitis and fibromyalgia. At least 100 allelic variants of the polymorphic PI locus have been described with groups including associations with different A1AT plasma levels and functions. Treatments with purified A1AT preparations, obtained through pooled human plasma (augmentation therapy), have been proven to improve survival and disease-related quality of life, as well as, slow down the progression of organ damage. Furthermore, ongoing research is now focusing on the development of specifically targeted, new medications. The aim of this review is to summarize our knowledge of the genetic A1AT variants, focusing on their variable clinical manifestation, report routine and recently updated laboratory diagnostic techniques, and to highlight the relevance of early diagnosis of A1ATD. Moreover, we will review the role of augmentation therapy recommendations and future perspectives focusing on a personalized treatment of A1ATD.

Short-term effects of a vibrotactile neck-based treatment device for positional obstructive sleep apnea: preliminary data on tolerability and efficacy.

BACKGROUND Positional supine obstructive sleep apnea syndrome (OSAS) characterizes a subgroup of patients suffering from OSAS. Several devices designed to limit supine position have been developed, but evidences of their efficacy and safety are lacking. It is unclear whether a neck-worn vibrating device could induce positional change in patients with positional OSAS. We evaluated the efficacy of a neck-worn device to induce supine avoidance positional feedback over a short-term trial in OSAS patients and its impact on sleep quality and polysomnographyc indexes. METHODS Twenty patients with positional apneas/hypopneas were prospectively studied. Baseline characteristics of daytime somnolence and risk of sleep apnea were screened and the efficacy of a 3-day trial of supine-avoidance therapy by vibrotactile neck worn device assessed by reporting the self-perceived change in quality of sleep and performing cardio-respiratory polysomnography. Comparison between baseline and treatment results was performed. RESULTS The neck device produced a reduction in overall apnea-hypopnea index (AHI) (mean AHI pre =16.8/h and post =4.4/h, P<0.0001), oxygen desaturation (pre =13.7/h and post =3.8/h, P<0.0001) and Respiratory Disturbance Indexes (RDI) (20.0/h vs. 5.2/h; P<0.0001).The time spent in supine position decreased from 62.1% to 33.7% of the total (P<0.001). However, the impact on the perceived quality of sleep was unpredictable. CONCLUSIONS The neck position therapy device is effective in restricting supine sleep, improving AHI and related polysomnographic indexes. However, at least in a short-term trial, it seems unable to improve the patients sleep quality.

The Extract of Leonurus sibiricus Transgenic Roots with AtPAP1 Transcriptional Factor Induces Apoptosis via DNA Damage and Down Regulation of Selected Epigenetic Factors in Human Cancer Cells

The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels. Additionally, we demonstrated differences in the content of compounds in the tested extracts by HPLC analysis with ATPAP1 construct and without. Both the tested extracts showed anticancer properties and the better results were observed for AtPAP1 with transcriptional factor root extract; this effect could be ascribed to the presence of higher condensed phenolic acids such as neochlorogenic acid, chlorogenic acids, ferulic acid, caffeic acid and p-coumaric acid. Further studies with AtPAP1 (with the transcriptional factor from Arabidopisi thaliana) root extract which showed better activities in combination with anticancer drugs are needed.

Screening of Obstructive Sleep Apnea Syndrome by Electronic-Nose Analysis of Volatile Organic Compounds

Obstructive Sleep Apnea Syndrome (OSAS) carries important social and economic implications. Once the suspicion of OSAS has arisen, Polysomnography (PSG) represents the diagnostic gold standard. However, about 45% of people who have undergone PSG are free from OSAS. Thus, efforts should be made to improve the selection of subjects. We verified whether the pattern of Volatile Organic Compounds (VOCs) helps to select patients amenable to PSG. We studied 136 subjects (20 obese non-OSAS, 20 hypoxic OSAS, 20 non-hypoxic OSAS, and 20 non-hypoxic Chronic Obstructive Pulmonary Disease (COPD) vs 56 healthy controls) without any criteria of exclusion for comorbidity to deal with a real-life population. VOCs patterns were analyzed using electronic-nose (e-nose) technology. A Discriminant Analysis (Partial Least Square-Discriminant Analysis) was performed to predict respiratory functions and PSG parameters. E-nose distinguished controls (100% correct classification) from others and identified 60% of hypoxic, and 35% of non-hypoxic OSAS patients. Similarly, it identified 60% of COPD patients. One-by-one group comparison yielded optimal discrimination of OSAS vs controls and of COPD vs controls (100% correct classification). In conclusion, e-nose technology applied to breath-analysis can discriminate non-respiratory from respiratory diseased populations in real-life multimorbid populations and exclude OSAS. If confirmed, this evidence may become pivotal for screening purposes.

Chest ultrasonography in health surveillance of asbestos related pleural disease

High resolution computed tomography, (HRCT), is currently considered the diagnostic gold standard to diagnose early stage malignant pleural mesothelioma and other non-malignant pleural conditions, but it is expensive and exposes the patient to radiation dose. In a screening and population medicine perspective, Thoracic Ultrasounds may become a valuable alternative because it can detect minimal changes in pleural surface, is widely available and safe. On these bases, we therefore validated thoracic US in subjects with history of exposure to asbestos, having HRCT as the reference standard. One hundred-fifty subjects were screened and 117 were recruited. Pleural abnormalities at US and/or HRCT were detected in 66 out of 117 subjects (prevalence=57%), and their prevalence was unrelated to both mansion and smoking habit, while mean age and mean length of exposure were higher in those having pleural abnormalities (age=47±5 vs 44±6years, p<0.05;years of exposure=20±7 vs 17±5, p<0.05). Thirteen out of 19 subjects with pleural abnormalities at HRCT were also identified by thoracic US, whereas 47 participants had lesions seen at US, but not at the HRCT scan. Positive and negative percent agreement were 66.6% and 51.8%, respectively; the McNemars test for equality showed a p-value <0.001. In conclusion, chest US might complement HRCT in the health surveillance of asbestos exposed population to detect earlier lesions or to follow up US approachable lesions. Further research is needed to clarify whether this approach may enhance early recognition of pleural mesothelioma and ameliorate prognosis.

Short term effects of neck-based treatment and monitoring device for positional obstructive sleep apnea

Introduction: positional components characterize a subgroup of patients suffering from obstructive sleep apnea syndrome (OSAS). Devices designed to limit supine position have been recently developed,but definitive evidence of their efficacy is lacking. In particular, no data exist related to a neck-worn vibrating device (Night shift™)intended to induce positional change in patients with positional OSA. We evaluated the efficacy of a neck-worn device by measuring snoring,sleep/wake time,time supine,and the frequency and duration of feedback to monitor compliance. Materials and Methods: 15 patients(13 males;mean age 65.9;SD 7.2;BMI 31.1-SD 2.0),with a mean apnea-hypopnea index (AHI) of 19.1 (SD 9.2) and high prevalence of positional apneas/hypopneas were prospectively studied.The efficacy of a 3 days trial of in-home supine-avoidance therapy by Night shift™ was assessed by self reported questionnaire and polysomnography. Results: in all participants the neck device produced a significant reduction in overall AHI,(mean delta-AHI of 19.1 and 3.5, respectively-p Conclusions: based on a short term trial, the neck position therapy device Night shift™ is effective in restricting supine sleep, improving AHI, and related polisomnographic indexes. However it seems unable to provide a relevant improvement in patient9s sleep quality. Larger population sample and longer follow up are needed.

Lung function prior to stem cell transplant as a predictor of infectious and pulmonary complications and survival in adults with haematologic malignancies

Introduction: autologous stem cell transplantation (ASCT) represents a standard of care for multiple myeloma patients eligible for high-dose therapy, for lymphoma patients undergoing second line treatments and in acute leukemia. Pulmonary and infective complications are a cause of morbidity and mortality after ASCT.While several reports focusing on allogenic transplantation exist,the relationship between pre-transplant pulmonary function tests(PFTs)and development of post-ASCT complications and mortality is unknown. Materials and Methods: complete PFTs were obtained in 67 patients candidate to ASCT for hematological malignancies.Complication rate and survival were obtained and correlations with PFTs assessed. Results: of the 67 transplanted patients(mean age 53.4,SD11.1),47(70%)were males;9(13.4%)had abnormal PFTs at baseline.Effects of ASCT were:partial response in 42(64.6%),complete remission in 17(26.2%),disease progression in 3(4.6%)and stable disease in 3(4.6%). Infective complications occurred in 40(59.7%)and respiratory complications in 9(13.4%).The overall survival rate was 71%(48/67-median follow up:25 months).Mean FEV1 percent of predicted pre ASCT resulted reduced(97%vs83%;p=0.05)in patients with post ASCT respiratory complications,while DLCO and KCO were lower(45.6vs59.0% of predicted;p=0.02)in patients who did not survive. Conclusions: abnormal pre ASCT FEV1 increased the risk of respiratory complications after ASCT,depressed DLCO and KCO the risk of death.These patients may benefit from modified transplant strategies to reduce morbidity and mortality.

Effects of topical therapy on the breath pattern of patients with newly diagnosed COPD: An e-nose based study

Introduction: In COPD,pulmonary and systemic inflammation,hypoxemia and cellular oxidative stress contribute to shape the pattern of exhaled volatile compounds (VOCs).One of the technologies to assess this pattern, known as electronic nose (e-nose), has been proved able to identify breath patterns of COPD patients and to differentiate them from healthy controls and selected other pulmonary or systemic diseases. It is unknown whether an e-nose can detect changes in VOCs determined by topical therapy.We aimed at verifying whether the breath print of untreated COPD patients obtained by an e-nose differed after a 12 weeks treatment with a single inhaled bronchodilator or a combination of bronchodilator and steroid. Materials and methods: twenty-five recently diagnosed and untreated COPD patients underwent a multidimensional assessment and e-nose based breath print analysis. Patients were therefore prescribed a conventional inhaled regimen according to current international guidelines and re-evaluated after a 12 week therapeutic trial. Results: breathprints from COPD patients after treatment were correctly discriminated from baseline in 24 out of 25 (84%) while nine out of 25 (36%) baseline breathprints were erroneously classified as belonging to the post treatment group. The overall accuracy was 74%. Conclusions: changes of breath composition induced by topic medications in COPD was fairly able to identify the sample of treated individuals.This finding support the effect on inhaled medications on breathprint composition of COPD patients and the potential role of exhaled breath analysis for assessing compliance to treatment and monitoring the effect of medications in COPD.