Clusters of individuals recovering from an exacerbation of chronic obstructive pulmonary disease and response to in-hospital pulmonary rehabilitation.

INTRODUCTION AND OBJECTIVES: Due to the present low availability of pulmonary rehabilitation (PR) for individuals recovering from a COPD exacerbation (ECOPD), we need admission priority criteria. We tested the hypothesis that these individuals might be clustered according to baseline characteristics to identify subpopulations with different responses to PR. METHODS: Multicentric retrospective analysis of individuals undergone in-hospital PR. Baseline characteristics and outcome measures (six-minute walking test - 6MWT, Medical Research Council scale for dyspnoea -MRC, COPD assessment test -CAT) were used for clustering analysis. RESULTS: Data analysis of 1159 individuals showed that after program, the proportion of individuals reaching the minimal clinically important difference (MCID) was 85.0%, 86.3%, and 65.6% for CAT, MRC, and 6MWT respectively. Three clusters were found (C1-severe: 10.9%; C2-intermediate: 74.4%; C3-mild: 14.7% of cases respectively). Cluster C1-severe showed the worst conditions with the largest post PR improvements in outcome measures; C3-mild showed the least severe baseline conditions, but the smallest improvements. The proportion of participants reaching the MCID in ALL three outcome measures was significantly different among clusters, with C1-severe having the highest proportion of full success (69.0%) as compared to C2-intermediate (48.3%) and C3-mild (37.4%). Participants in C2-intermediate and C1-severe had 1.7- and 4.6-fold increases in the probability to reach the MCID in all three outcomes as compared to those in C3-mild (OR = 1.72, 95% confidence interval [95% CI] = 1.2 - 2.49, p = 0.0035 and OR = 4.57, 95% CI = 2.68 - 7.91, p < 0.0001 respectively). CONCLUSIONS: Clustering analysis can identify subpopulations of individuals recovering from ECOPD associated with different responses to PR. Our results may help in defining priority criteria based on the probability of success of PR.

Oxidative stress, inflammation and disease activity biomarkers in lupus nephropathy.

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and ß2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers (P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.

Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma.

BACKGROUND: Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year. METHODS: Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, exacerbations, hospitalizations, oral corticosteroids use were also collected at the same time points. RESULTS: A statistically significant reduction at T1, T2 and T12 of nerve fibers was observed in the submucosa and in ASM compared to T0. Among inflammatory cells, only CD68 showed significant changes at all time points. Improvement of all clinical outcomes was documented and persisted at the end of follow up. CONCLUSIONS: A reduction of nerve fibers in epithelium and in ASM occurs earlier and persists at one year after BT. We propose that nerve ablation may contribute to mediate the beneficial effects of BT in severe asthma. TRIAL REGISTRATION: Registered on April 2, 2013 at ClinicalTrials.gov Identifier: NCT01839591 .

Federico Milá de La Roca: un personaje inolvidable / Federico Milá de la Roca: an unforgettable character

En este artículo se presenta una semblanza de la vida y obra del Dr. Federico Milá de la Roca, médico venezolano, quien fue uno de los fundadores del Instituto Nacional de Higiene, resaltando diferentes rasgos de su personalidad y sus destacadas actuaciones en el campo profesional y personal.

This paper presents a brief biography of Federico Milá de la Roca, Venezuelan medical doctor, who was one of the founders of the Instituto Nacional de Higiene, highlighting various features of his personality and outstanding performances related with his personal and profesional life.

[Questionnaires for occupational disability evaluation in patients with chronic respiratory diseases]. / Questionari per la valutazione della disabilità occupazionale in pazienti con malattie respiratorie croniche.

Chronic Obstructive Pulmonary Disease (COPD) represents a model of respiratory degenerative chronic disabling disorder. In Pulmonary Rehabilitation (PR), occupational approach is aimed at restoring patient's abilities at best in the social, familiar and working scenarios, and it is an essential part of a good PR Programme. To evaluate first occupational disability and then the occupational outcome of a PR programme, we need appropriate tools. London Chest Activity of Daily Living (LCADL) ed il Manchester Respiratory Activities of Daily Living (MRADL) are two questionnaires with such characteristics available in the literature. Our aim was to translate into Italian and adapt to the Italian social reality these two questionnaires. This may be a preliminary albeit necessary step to obtain reliable data on the occupational outcome of PR programmes in Italy.

Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD.

BACKGROUND: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. OBJECTIVES: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. METHODS: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). RESULTS: The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2-15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils co-expressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. CONCLUSION: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.

T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients.

There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)-17 as their effector cytokine under the control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)-17A, IL-17F, IL-21, IL-22 and IL-23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age-matched control subjects. The expression of IL-17A, IL-17F, IL-21, IL-22, IL-23 and RORC2 was measured in the bronchial mucosa using immunohistochemistry and/or quantitative polymerase chain reaction. The number of IL-22(+) and IL-23(+) immunoreactive cells is increased in the bronchial epithelium of stable COPD compared with control groups. In addition, the number of IL-17A(+) and IL-22(+) immunoreactive cells is increased in the bronchial submucosa of stable COPD compared with control non-smokers. In all smokers, with and without disease, and in patients with COPD alone, the number of IL-22(+) cells correlated significantly with the number of both CD4(+) and CD8(+) cells in the bronchial mucosa. RORC2 mRNA expression in the bronchial mucosa was not significantly different between smokers with normal lung function and COPD. Further, we report that endothelial cells express high levels of IL-17A and IL-22. Increased expression of the Th17-related cytokines IL-17A, IL-22 and IL-23 in COPD patients may reflect their involvement, and that of specific IL-17-producing cells, in driving the chronic inflammation seen in COPD.

Tele-assistance in chronic respiratory failure patients: a randomised clinical trial.

Chronic respiratory patients requiring oxygen or home mechanical ventilation experience frequent exacerbations and hospitalisations with related costs. Strict monitoring and care have been recommended. The aim of the present study was to primarily evaluate reduction in hospitalisations and, secondly, exacerbations, general practitioner (GP) calls and related cost-effectiveness of tele-assistance (TA) for these patients. A total of 240 patients (101 with chronic obstructive pulmonary disease (COPD)) were randomised to two groups: an intervention group entered a 1-yr TA programme while controls received traditional care. No anthropometric and clinical differences were found between groups both in baseline and in mortality (18% for TA, 23% for controls). Compared with controls, the TA group experienced significantly fewer hospitalisations (-36%), urgent GP calls (-65%) and acute exacerbations (-71%). Only COPD patients, as a separate group, had fewer hospitalisations, emergency room admissions, urgent GP calls or exacerbations. Each patient referred to staff a mean+/-sd 36+/-25 times. After deduction of TA costs, the average overall cost for each patient was 33% less than that for usual care. In chronic respiratory failure patients on oxygen or home mechanical ventilation, a nurse-centred tele-assistance prevents hospitalisations while it is cost-effective. The chronic obstructive pulmonary disease group seems to have a greater advantage from tele-assistance.

Evolución histórica y logros de la gerencia sectorial de producción del Instituto Nacional de Higiene Rafael Rangel / Historical evolution and achievements of the sector's production management of the Instituto Nacional de Higiene Rafael Rangel

La Gerencia Sectorial de Producción elabora vacunas bacterianas y virales de uso humano y veterinario, para satisfacer necesidades específicas de nuestra población. Igualmente responde a los requerimientos del resto de las áreas técnicas de la institución, a las que provee de insumos, reactivos químicos y biológicos como cultivos celulares y animales de experimentación, entre otros. También presta servicios con fines diagnósticos, productivos, de control e investigación. Un ejemplo relevante de proyección de la Gerencia Sectorial de Producción, y del Instituto, lo constituye la nueva Planta de Vacunas, instalación de alta tecnología que representa un contundente aporte para consolidar la autosuficiencia nacional en la producción de tan importantes rubros para la salud.

The Sectorial Productión Management produces bacterial and viral vaccines for human and veterinary use to satisfy specific needs of our population. It also responds, to the requirements of the rest of the technical units of the Institute, to whom it provides with chemical and biological reagents like cellular cultures and laboratory animals, among others. It also carry out activities for diag nostic purposes, production, control and research. An excellent example of projection of The Sectorial Productión Management and the Institute constitutes the new Vaccine Plant, installation of high technology that will allow to consolidate the national self-sufficiency in the production of such important headings for the health.

Home mechanical ventilation patients: a retrospective survey to identify level of burden in real life.

BACKGROUND AND AIM: Home care for patients under home mechanical ventilation (HMV) may cause dramatic physical and economic burden in addition to the burden of time on family/caregivers and health care service (HCS) with difficult resource allocation decision-making. Our aims were: 1. To identify conditions causing major care burden in managing HMV patients according to family and payer's perspectives related to characteristics of the disease, dependency and accessibility; and 2. To find, if any, differences among diseases. METHODS: A questionnaire was sent to eight pulmonary centres to identify factors connected with the greater care burden. Retrospective data of 792 patients still alive and in HMV was reviewed. RESULTS: Compared to neuromuscular disorders (NM) and chest wall deformities, the COPD group have presented a statistically greater number of hospitalisations/yr (1.37 +/- 0.77), greater length of stay (13 +/- 10 days), higher number of outpatient visits/yr (2.55 +/- 1.73) or emergency room accesses/yr (0.74 +/- 1.08). Patients with NM diseases need more home care. The prevalence of one, two and three among five selected burden criteria (needs of MV > 12 hrs/day, tracheotomy, high dependency, distance from hospital, frequent hospitalisations) was respectively 19%, 30% and 33% of the cases; the NM was the group most represented. CONCLUSIONS: In HMV patients: 1. underlying disease, level of their dependency, hours spent under MV, presence of tracheotomy, home distance from hospital, hospital accesses are the causes of major care burden; and 2. as a novelty we have demonstrated that more than fifty percent of them present two or three contemporaneous criteria selected as care burden, being NM and COPD patients the most representative group necessitating of family's and HCS's care respectively.

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults.

Bronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7 x 10(6).mL(-1) total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.

Efficacy of pulmonary rehabilitation in chronic respiratory failure (CRF) due to chronic obstructive pulmonary disease (COPD): The Maugeri Study.

UNLABELLED: While the effectiveness of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) is well established, its effectiveness in the most severe category of COPD, i.e. patients with chronic respiratory failure (CRF), is less well known. OBJECTIVE: To verify the effects of PR in patients with CRF, and compare the level of improvement with PR in these patients to that of COPDs not affected by CRF. METHODS: A multi-centre study was carried out on COPD patients with versus without CRF. The PR program included educational support, exercise training, and nutritional and psychological counselling. Lung function, arterial gases, walk test (6MWT), dyspnoea (MRC; BDI/TDI), and quality of life (MRF(28); SGRQ) were evaluated. RESULTS: Thousand forty seven consecutive COPD inpatients (327 with CRF) were evaluated. In patients with CRF all parameters improved after PR (0.001). Mean changes: FEV(1), 112 ml; PaO(2), 3.0 mmHg; PaCO(2), 3.3 mmHg; 6MWT, 48 m; MRC, 0.85 units; MRF(28) total score, 11.5 units. These changes were similar to those observed in patients without CRF. CONCLUSIONS: This study, featuring the largest cohort so far reported in the literature, shows that PR is equally effective in the more severe COPD patients, i.e. those with CRF, and supports the prescription of PR also in these patients.

A pilot study of nurse-led, home monitoring for patients with chronic respiratory failure and with mechanical ventilation assistance.

We assessed the feasibility of telemedicine for home monitoring of 45 patients with chronic respiratory failure (CRF) discharged from hospital. The patients transmitted pulsed arterial saturation (pSat) data via a telephone modem to a receiving station where a nurse was available for a teleconsultation. A respiratory physician was also available. Scheduled and ad hoc appointments were conducted. Thirty-five patients were on home mechanical ventilation, 13 with invasive and 22 with non-invasive devices. The main diagnosis was chronic obstructive pulmonary disease (COPD). The follow-up period was 176 days (SD 69). In all, 376 calls for scheduled consultations were received and 83 ad hoc consultations were requested by the patients. The actions taken were: 55 therapy modifications, 19 hospitalizations in a respiratory department for decompensated CRF, three hospitalizations in an intensive care unit (ICU), 22 requests for further investigations, 25 contacts with the general practitioner (GP), 66 demands for respiratory consultations and 10 calls for the emergency department. The mean time recorded for the 459 calls was 16 min/patient/week. In 82% of calls, a pSat recording was received successfully. The nurse time required to train the users in the operation of the pSat instrument was high (mean time 30 min). However, the results showed that home monitoring was feasible, and useful for titration of oxygen, mechanical ventilation setting and stabilization of relapses.

Maximal inspiratory and expiratory pressure measurement in tracheotomised patients.

The present study compared four different sites and conditions for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28 had chronic obstructive pulmonary disease (COPD). The four different conditions were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed cannula (condition C); and 4) through the mouth after stoma closure (condition D). Five trials in each condition were performed using a standardised method. The measurement of both MIP and MEP differed significantly depending on the condition of measurement. MIP taken in condition A was significantly higher when compared with conditions B, C and D. MEP in condition A was significantly higher when compared with condition B and D. In condition A the highest frequency of the best measurement of MIP and MEP was observed at the fourth and fifth effort, respectively. The same results were obtained after the selection of only COPD patients. In conclusion, respiratory muscle assessment differs significantly depending on measurement condition. Measurement through inflated cannula tracheotomy yields higher values of both maximal inspiratory and maximal expiratory pressure.