Massimo Guerriero

A Two-Stage Logistic Model Based on the Measurement of Pro-Inflammatory Cytokines in Bronchial Secretions for Assessing Bacterial, Viral, and Non-Infectious Origin of COPD Exacerbations

Exacerbations often complicate the progressive course of chronic obstructive pulmonary disease (COPD), mainly due to infectious agents. The precise role of bacterial infections in the course and the pathogenesis of COPD has been a source of controversy for decades. Also viruses and other non-infectious causes of exacerbation play a relevant role and also contribute to persisting airway inflammation. Usually, the etiologic identification of the infective causes of COPD require considerable time and costs. The development of more rapid, reliable, and widely applicable methods to promptly define the etiology of COPD exacerbations should represent a relevant issue in devising earlier and more specific strategies for their effective therapeutic control. Aim: of the study was to assess the predictive role of some pro-inflammatory cytokines measured in spontaneous bronchial secretions in discriminating the main infectious causes of COPD exacerbations. Methods: 124 subjects with moderate COPD (51–79 y; mean basal FEV1 = 49.6% pred. ± 4.6 sd; FEV1 reversibility + 3.9% from baseline ± 4.8 sd after salbutamol 200 mcg) were studied during acute exacerbation. Respiratory viruses were isolated from bronchial secretions in 21 cases; common bacteria (CFU ≥ 106/ml) in 28 cases; Pseudomonas Aeruginosa (Ps.Ae.; CFU ≥ 106/ml) in 20 cases. The cytokines IL1β, IL8, and TNFα (pg/ml; Immulite; Diagnostic Product Corp, Los Angeles, CA, USA), and neutrophils (% total count) were measured in bronchial secretions of all patients. Statistics: a two-stage logistic model was chosen for discriminating the different causes of COPD exacerbations (such as: non-infectious, or viral, bacterial, or due to Ps.Ae.). Results: At the first decisional step, the two-stage logistic model proved that TNFα levels in bronchial secretions recognise clearly patients belonging to the Ps.Ae. group from those of all othergroups (Area under ROC curve = 0.96; 95% CI = 0.91–0.99), and that, at the second decisional step, IL8 + IL1β levels discriminate patients with bacterial causes (such as all bacteria) from the non-infected ones and from those with a viral cause of exacerbation (Area under ROC curve = 0.87; 95% CI = 0.77–0.94). Neutrophil percent count did not support any contribution in discriminating the different subgroups of COPD subjects. Conclusions: when exacerbated, COPD subjects express different patterns of pro-inflammatory mediators in bronchial secretions, which appear modulated according to the etiological cause of the exacerbation. In particular, TNFα concentration per se enables recognition of COPD exacerbations due to Ps.Ae., while IL8 + IL1β levels prove helpful in discriminating those to common bacteria from those to viral agents and to non-infectious causes. When present data are further confirmed, the use of a decisional rule based on cytokine measurements might be regarded as a helpful predictive tool. As measures of pro-inflammatory cytokines are low-cost, simple, and faster to perform, they could support rapid clinical decision making at the bedside regarding therapeutic strategy for COPD exacerbations, in particular when they are needed for severe COPD patients.

Prevalence of tracheobronchomalacia and excessive dynamic airway collapse in bronchial asthma of different severity

BackgroundTracheobronchomalacia (TBM) is a pathologic condition in which softening of tracheal and bronchial cartilage causes the dynamic narrowing of transverse or sagittal diameters of tracheobronchial lumen; an excessive dynamic airway collapse (EDAC) may also be associated, with a substantial invagination of the posterior membrane of trachebronchial tree.The aim of this study was to assess the prevalence of both TBM and EDAC in a population of asthmatics with different degrees of disease severity compared to a reference group of subjects without any bronchial obstruction.MethodsA cohort of 202 asthmatics was investigated by means of a dynamic flexible videobronchoscopy: 74 mild persistent (MPA - age 18–68 ys; 35 males; mean FEV1 = 88.6% pred. ± 8.3 sd); 63 moderate (MA - age 21–71 ys; 30 males; mean FEV1 = 71.3% pred. ± 9.1 sd), 65 severe asthmatics (SA - age 33–70 ys; 25 males; mean FEV1 = 48.5% pred. ± 7.6 sd), and 62 non obstructed subjects (NO - age 18–71 ys; 38 males; mean FEV1 98.6% pred. ± 2.7 sd). TBM and EDAC were classified according to FEMOS classification.ResultsTBM and EDAC were observed in only 1/62 subjects (both 1.61%) of NO group, while their prevalence was 2.70% and 6.75% in MPA group; 7.93% and 19.04% in MA group; 18.46% and 69.23% in SA group, respectively. The crude prevalence of thyroid disorders in the population was 12.9%. In particular, the prevalence of thyroid disorders was significantly higher in females than in men, but 54-fold higher in females than in men in the presence of EDAC.Conclusions1) The prevalence of both TBM and EDAC is directly related to age, gender (females), and asthma severity; 2) EDAC is much more frequent than TBM in all asthma patients; 3) both tracheal abnormalities proved to be more represented in asthmatics with thyroid disorders, and particularly in female asthmatics with EDAC.

Intravitreal Dexamethasone Implant for Macular Edema Secondary to Retinal Vein Occlusion: 12-month Follow-Up and Prognostic Factors

Purpose: To evaluate anatomical and visual outcomes following intravitreal dexamethasone implantation (Ozurdex) in eyes with visual loss due to macular edema (ME) secondary to retinal vein occlusion (RVO) and to identify predictive factors for improvement in best-corrected visual acuity (BCVA). Methods: We retrospectively analyzed medical records of 43 consecutive eyes with treatment-naïve ME secondary to recent onset RVO treated with repeated Ozurdex injections on a pro re nata basis. Results: The mean follow-up (FU) duration was 14 months (min. 12, max. 22). Both mean BCVA and central macular thickness improved significantly at the end of the FU period (p = 0.0001), and more than 30% of the eyes gained ≥3 lines within 3 months of repeated injections. Presence of foveal serous retinal detachment and macular ischemia were negatively associated with visual outcomes. Improvements were significantly associated with baseline BCVA and the integrity of the ellipsoid zone. No serious adverse events were recorded. Conclusions: In our study population, Ozurdex was a safe and effective therapeutic option for the treatment of ME associated with RVO. The results suggest that a comprehensive approach in the examination of RVO eyes may help to predict which patients are most likely to benefit from the treatment.

Changes in total IgE plasma concentration measured at the third month during anti-IgE treatment predict future exacerbation rates in difficult-to-treat atopic asthma: a pilot study.

In severe, difficult-to-treat atopic asthma with sensitization to perennial allergens, monoclonal antibodies directed against immunoglobulin E (IgE) are recognized to be clinically effective. Omalizumab, a recombinant monoclonal antibody, selectively binds to the high-affinity C-epsilon 3 site of human IgE and inhibits the inflammatory cascade in response to antigenic stimuli. Currently, no indicator is available for predicting patients’ responsiveness to long-term omalizumab treatment. This study aims to assess the relationship between early changes in plasma IgE concentration and major outcome variables over a 12-month course of omalizumab. Methods. Twenty-three nonsmoking, severe asthmatics (14 females; mean age 47.3 years ± 12.0 SD; mean BMI 25.8 kg/m2 ± 9.6 SD) sensitized to perennial allergens and unresponsive to high doses of common therapies were evaluated during a 12-month period of omalizumab treatment. Variables included total IgE plasma concentrations, Forced Expiratory Volume 1 second (FEV1) symptom complaints (Asthma Control Test (ACT) score), number of emergency visits, hospitalizations, and exacerbations. The Wilcoxon signed-rank test was used to compare changes observed after the 1-year omalizumab treatment versus baseline. Statistical modelization was used to determine possible relationships between changes in outcomes after 12 months and early changes in plasma IgE (after 3 months of treatment). Results. The number of emergency visits, hospitalizations, and exacerbations decreased (p < .004, p < .001, and p < .001, respectively) over the 12-months. In contrast, FEV1 and ACT score substantially increased (both p < .001); the ACT score reaching maximum after only 3 months. The S model showed the best fit and proved the strict relationship between the increase in IgE after 3 months and the exacerbation rate over the 1-year survey (threshold value of ≥250 IU/ml, p < .001). The improvement in FEV1 was independent of the increase in IgE. Conclusions. When confirmed on a larger population, early changes in IgE may be used as a predictor of future responders to omalizumab in terms of exacerbation rate, thus minimizing the economic burden of anti-IgE therapy.

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

Background Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

Respiratory symptoms/diseases prevalence is still increasing: a 25-yr population study

BACKGROUND Few epidemiological surveys on general population samples estimated changes in prevalence of respiratory symptoms/diseases over a long time interval; our study aims to quantify the temporal changes in the prevalence rates of asthma, allergic rhinitis and Chronic Obstructive Pulmonary Disease (COPD) after 25 years from baseline. METHODS A general population sample participated in 3 cross-sectional surveys carried out in Central Italy (Pisa) in 1985-88 (n = 3865), 1991-93 (n = 2841), 2009-11 (n = 1620). 2276 (47%) subjects participated in at least 1 survey, 1723 (35.5%) in at least 2 surveys and 849 (17.5%) in all the 3 surveys. All subjects filled in a standardized questionnaire about health status and risk factors; a sub-sample performed spirometry. Chi-square test was used to compare adjusted prevalence rates of respiratory symptoms/diseases and descriptive characteristics among the surveys. Generalised estimating equations (GEE) were used to analyze the association between respiratory symptoms/diseases and risk factors. RESULTS There was an increasing trend in prevalence rates of all respiratory symptoms/diseases throughout the surveys: current asthma attacks (1st-3rd survey prevalence: 3.4-7.2%), allergic rhinitis (16.2-37.4%), usual phlegm (8.7-19.5%) and COPD (2.1-6.8%) more than doubled. The GEE model confirmed these increasing trends, indicating higher risk of having respiratory symptoms/diseases in the second and third surveys. CONCLUSIONS While asthma and allergic rhinitis increasing trends were confirmed, with respect to other international studies, also a COPD increasing prevalence rates was shown.

COPD prevalence in a north-eastern Italian general population

BACKGROUND COPD prevalence estimates vary mostly depending on different study methodologies. We evaluated the prevalence and clinical features of COPD, as defined by GOLD and ERS/ATS recommendations in a representative sample of Northern Italy general population. METHODS A randomized cross-sectional study was performed. The study participants completed a questionnaire covering: key indicators for considering a diagnosis of COPD, self-reported physician diagnoses of respiratory disease, pharmacological treatment for respiratory disease, indirect costs, occupational and environmental exposures. They also underwent spirometry and physician assessment. RESULTS We evaluated 1236 subjects. Daily respiratory symptoms were experienced by 26.7%. Of this group, only 30.7% had previously performed a spirometry. The overall COPD prevalence was: 11.7% according to GOLD criterion; 9.1% according to LLN criterion; 6.8% according to self-reported physician diagnosis. Of note, 48,8% of subjects with a reported diagnosis of COPD had never undergone a spirometry before the study. CONCLUSIONS Our study provides an estimation of COPD prevalence in a representative sample of Northern Italy general population relying on both clinical symptoms and spirometry outcomes, and describes the different prevalence rates depending on the adopted diagnostic criterion. Spirometry underuse may account for under-diagnosis and misdiagnosis of COPD. It may result in a major impact on quality of life as well as in economic burden.

Long-Term Results of Full Macular Translocation for Choroidal Neovascularization in Age-Related Macular Degeneration

PURPOSE To investigate the long-term outcome of full macular translocation (FMT) for neovascular age-related macular degeneration (AMD) and to identify predictive factors. DESIGN Retrospective, uncontrolled case series. PARTICIPANTS Patients were considered for FMT if they had low vision in the fellow eye and choroidal neovascularization (CNV) along with (1) no response to vascular endothelial growth factor (VEGF) inhibitors, (2) retinal pigment epithelium (RPE) tear, (3) subretinal hemorrhage, (4) foveal scar tissue of recent onset, or (5) CNV before the availability of VEGF inhibitors. From 2004 through 2012, a total of 255 patients underwent FMT. Exclusion criteria were patients younger than 60 years, FMT for disease other than AMD, and a follow-up of less than 12 months. METHODS Preoperative, annual, and last distance best-corrected visual acuity (BCVA) were obtained retrospectively from patient files. Complications were recorded using funduscopy, optical coherence tomography, autofluorescence, and angiography. MAIN OUTCOME MEASURES Distance BCVA at 1 year and 5 years after surgery and at last visit compared with preoperative BCVA. RESULTS One hundred fifty-eight patients (mean follow-up, 45 months) were included. Median BCVA improved from 0.90 logarithm of the minimum angle of resolution (logMAR) before surgery to 0.70 logMAR 1 year after FMT (2 lines gained; P = 0.000). In a subgroup of 56 patients followed up for 5 years or more, median BCVA improved from 0.95 logMAR before surgery to 0.70 logMAR 1 year after surgery, and remained improved 5 years after FMT with a median BCVA of 0.80 logMAR (1.5 lines gained compared with preoperative BCVA; P = 0.000). The main complications were foveal RPE atrophy (n = 73; 47%) and CNV recurrence (n = 47; 30%). Foveal RPE atrophy (odds ratio [OR], 7.0), CNV recurrence (OR, 2.6), and proliferative vitreoretinopathy (PVR; OR, 17.6) were statistically significant predictors (P < 0.05) for losing 1 line or more at last visit. CONCLUSIONS In this study, BCVA was improved up to 5 years after FMT. Foveal RPE atrophy, CNV recurrence, and PVR carried a worse prognosis. In patients who are unlikely to benefit from VEGF inhibitors, FMT can be considered for second eyes with neovascular AMD.

A MCh Test Pre-post Esophageal Acidification in Detecting GER-related Asthma

The direct effect of gastro-esophageal reflux (GER) on lung function is still debated. Objective. To investigate the role of esophageal acidification in affecting airway response to MCh in GER-related versus atopic asthmatics and to assess specificity and sensitivity of events. Subjects. A total of 56 never-smoking, mild asthmatics: 27 non-atopic asthmatics and acid GER (GER+ve) and 29 atopic asthmatics without any GER (GER–ve). Methods. Each subject performed an MCh challenge in baseline (MChb), and 30 minutes after an acid drink (125 mL at pH = 2; MChac), one day apart. PD20FEV1 MChb and MChac were compared by estimating the area under the ROC curve (AU-ROC). Results. GER+ve and GER-ve subjects (well matched in baseline) had a different duration of esophageal acid contact (24-hour monitoring; pH-24h AU4), and PD20FEV1 MChac (both p < 0.001). AU-ROC was 86.3% (76% to 97%, 95%CI). Sensitivity and specificity of changes were 82.8% (72.9% to 92.7%, 95%CI) and 85.2% (75.9% to 94.5%, 95%CI), respectively. The difference in MCh threshold that maximized both the sensitivity and specificity level was 100 μ g. Conclusions. The esophageal acidification identified GER-related asthma with a good level of both sensitivity and specificity by enhancing the MCh response only in the presence of acid GER. Data are supporting the effectiveness of this procedure for clinical purposes.

Inverted Internal Limiting Membrane Flap Technique Versus Complete Internal Limiting Membrane Removal In Myopic Macular Hole Surgery: A Comparative Study

Purpose: To compare the results of vitrectomy with complete internal limiting membrane (ILM) removal and inverted ILM flap in the treatment of myopic macular hole (MMH). Methods: Seventy eyes of 68 patients with MMH undergone pars-plana vitrectomy (PPV) with either complete ILM removal (n = 36, Group 1) or inverted ILM flap technique (n = 34, Group 2) were included in the study. Outcomes measured were the rate of MMH closure assessed by optical coherence tomography (OCT) and visual acuity (BCVA) at six months. Results: Closure of MMH was achieved in 22 cases of Group 1 (61%) and in 32 cases of Group 2 (94%). Surgical failure was reported in 14 cases of Group 1 (39%) and in one case of Group 2 (3%). Average best-corrected visual acuity (BCVA) changed from 0.60 to 0.58 in Group 1 (P = 0.329) and from 0.70 to 0.39 in Group 2 (P < 0.01). Logistic regression analysis showed that inverted ILM flap technique was associated with 22 times higher probability of anatomic success, regardless of the MMH diameter. Conclusion: Inverted ILM flap should be preferred to complete ILM removal for the treatment of MMH. The outcomes reported with this technique were better than any other technique described until now.