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Bartolome Celli

Publications and source records attributed to Bartolome Celli.

13 recordsLinked to original sources
PubMed2026

New approaches to uncover COPD pathobiology and develop therapies.

Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

Humans↗
PubMed2006

Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD.

STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group study. PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal. INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50. RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Adrenergic beta-Agonists↗
PubMed2005

Future perspectives in COPD.

The pathophysiology of chronic obstructive pulmonary disease (COPD) is complex. The development of a multidimensional index--such as the BODE index--provides a means of classifying patients with COPD that also correlates with their prognosis. The individual components of the BODE index--body mass index (B), airflow obstruction (O) dyspnoea (D) and exercise capacity (E)--incorporate the pulmonary as well as the systemic effects seen in patients with COPD. Recent research has focussed on examining these impairments (including those of metabolism and inflammation) more carefully, and determining the effects of treatment on both the systemic and physiological aspects of COPD. Ongoing research initiatives by the public and private sector will contribute to our understanding of the disease processes underlying COPD, our understanding of the benefits associated with commonly used pharmacotherapies, as well as laying the foundations for the development of new agents and therapeutic tools. Advances in the use of pharmacotherapy have been mirrored by research to better define the benefits associated with pulmonary rehabilitation. Many questions remain to be answered, but a comprehensive approach is now considered essential to the life-long management of COPD, and will undoubtedly reduce the considerable socio-economic burden of COPD.

Adrenergic beta-Agonists↗
PubMed2004

Gene expression profiling of human lung tissue from smokers with severe emphysema.

The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of chronic obstructive pulmonary disease remains unknown. We used high-density microarrays to measure gene expression in severely emphysematous lung tissue removed from smokers at lung volume reduction surgery (LVRS) and normal or mildly emphysematous lung tissue from smokers undergoing resection of pulmonary nodules. Class prediction algorithms identified 102 genes that accurately distinguished severe emphysema from non-/mildly emphysematous lung tissue. We also defined a number of genes whose expression levels correlated strongly with lung diffusion capacity for carbon monoxide and/or forced expiratory volume at 1 s. Genes related to oxidative stress, extracellular matrix synthesis, and inflammation were increased in severe emphysema, whereas expression of endothelium-related genes was decreased. To identify candidate genes that might be causally involved in the pathogenesis of emphysema, we linked gene expression profiles to chromosomal regions previously associated with chronic obstructive pulmonary disease in genome-wide linkage analyses. Unsupervised hierarchical clustering of the LVRS samples revealed distinct molecular subclasses of severe emphysema, with body mass index as the only clinical variable that differed between the groups. Class prediction models established a set of genes that predicted functional outcome at 6 mo after LVRS. Our findings suggest that the gene expression profiles from human emphysematous lung tissue may provide insight into pathogenesis, uncover novel molecular subclasses of disease, predict response to LVRS, and identify targets for therapeutic intervention.

Aged↗
PubMed2004

Clinical trial design considerations in assessing long-term functional impacts of tiotropium in COPD: the UPLIFT trial.

An accelerated loss of lung function is one of the defining characteristics of chronic obstructive pulmonary disease (COPD). To date, the only successful intervention shown to conclusively attenuate the loss of lung function over time is smoking cessation. Pharmacological interventions including inhaled corticosteroids and ipratropium bromide have not altered the rate of decline of lung function. Tiotropium is an inhaled anticholinergic that provides 24-hour bronchodilation with once-daily dosing due to prolonged muscarinic M3 receptor blockade. Controlled clinical trials have suggested sustained efficacy for periods of up to one year. We therefore initiated a four-year, controlled clinical trial (UPLIFT, Understanding the Potential Long-Term Impacts on Function with Tiotropium) in patients with COPD to evaluate the long-term effects of tiotropium on the rate of decline in lung function and health status as well as the frequency of exacerbations. The design of such large, long-term clinical trials presents unique methodological challenges including the definition of endpoints, the quality and variability of spirometric measurements and premature patient discontinuations from the trial. The present manuscript outlines the rationale for the UPLIFT study, and reviews the study design and the steps taken to address methodological challenges experienced in other long term studies. Careful design and implementation of the UPLIFT trial is anticipated to yield high quality results that will help in increasing our understanding of the long term natural history of COPD in a global population as well as to elucidate the role that tiotropium can play in affecting the course of this debilitating disease.

Administration, Inhalation↗
PubMed2003

Electromyographic validation of the mouth pressure-time index: a noninvasive assessment of inspiratory muscle load.

The pressure-time index (PTI = Pmouth/Pi max x Ti/Ttot) has been validated by Ramonatxo (J. Appl. Physiol. 78 (1995) 646 and by Jabour (Am. Rev. Respir. Dis. 144 (1991) 531 as a noninvasive tool for the assessment of inspiratory muscles load. Nobody until now has evaluated the correlation between the PTI and diaphragmatic activity. Further, the PTI has not been compared with another measures of respiratory muscle load such as the transdiaphragmatic pressure index or TTdi. The purpose of our study was to test the hypothesis that the PTI measured at the mouth (PTIm) is a noninvasive reflection of TTdf and electromyographic activity of the diaphragm (EMGdf). We studied 6 patients with COPD and 5 normal individuals at rest and during a CO2 rebreathing trial and simultaneously measured PTIm, TTdi and EMGdi. The curves of PTIm and EMGdi follows the same trend during the CO2 rebreathing trial with strong and significant correlation between these parameters (r = 0.89 P < 0.05 and r = 0.82 P < 0.05 for PaCO2 of 45 and 53 mmHg respectively). We conclude that PTIm measured as Pmouth/Pi max x Ti/Ttot is an adequate noninvasive method that reflect not only the diaphragmatic activity but also the inspiratory muscles load.

Aged↗
PubMed2003

Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes.

BACKGROUND: In patients with COPD, changes in inspiratory capacity (IC) have shown a higher correlation to patient-focused outcomes, such as dyspnea with exercise, than other standard spirometric measurements. Changes in IC reflect changes in hyperinflation. Tiotropium is a once-daily inhaled anticholinergic that has its effect through prolonged M3 muscarinic receptor antagonism and has demonstrated sustained improvements in spirometric and health outcomes. We sought to evaluate changes in resting IC and lung volumes after long-term administration of tiotropium. METHODS: To evaluate the effect of tiotropium, 18 micro g/d, on IC, a 4-week, randomized, double-blind, placebo-controlled study was conducted in 81 patients with stable COPD. At each of the visits (weeks 0, 2, and 4) FEV(1), FVC, IC, slow vital capacity (SVC), and thoracic gas volume (TGV) were measured prior to study drug (- 60 and - 15 min) and after study drug (30 min, 60 min, 120 min, and 180 min). RESULTS: Mean age was 64 years; 62% were men. Mean baseline FEV(1) was 1.12 L (43% predicted). The mean differences (tiotropium - placebo) in FEV(1) trough (morning before drug), peak, and area under the curve over 3 h values (adjusted for baseline and center differences) at week 4 were 0.16 L, 0.22 L, and 0.22 L, respectively (p < 0.01 for all); differences in IC for these variables were 0.22 L, 0.35 L, and 0.30 L (p < 0.01 for all). Differences in TGV were - 0.54 L, - 0.60 L, and - 0.70 L, respectively (p < 0.01 for all). The percentage improvement in area under the curve above baseline with tiotropium was similar among FEV(1) and lung volumes (FEV(1), 18%; FVC, 20%; SVC, 16%; IC, 16%; TGV, 14%). CONCLUSIONS: Observed improvements in IC and reductions in TGV with once-daily tiotropium reflect improvements in hyperinflation that are maintained over 24 h.

Airway Resistance↗
PubMed2002

Physiologic responses to long-term ventilation.

Long-term MV, delivered by way of a tracheostomy or noninvasive mask, often is indicated in patients with restrictive or neuromuscular pulmonary diseases and occasionally in patients with severe obstructive hypercapnic respiratory failure. Regardless of the mode of ventilation, respiratory physiology seems to be significantly impacted in these patients. Although the effects of ventilation can be unpredictable, they often seem to be favorable. Selected patients can develop increased sensitivity to hypercapnia, with subsequent improvements in blood gas tensions and decreased pulmonary artery pressures, which result in augmented cardiac function and greater tolerance to exercise. The patient-ventilator interaction, mode of ventilation, and degree of support should be considered when managing these patients. For some patients, particularly patients with fibrotic lung disease or COPD, chronic MV likely does not alter pathophysiology or improve prognosis.

Chronic Disease↗
PubMed2002

Power of outcome measurements to detect clinically significant changes in pulmonary rehabilitation of patients with COPD.

STUDY OBJECTIVES: Several validated instruments are used to measure outcomes, such as exercise performance, dyspnea, and health-related quality of life after pulmonary rehabilitation (PR) in patients with COPD. However, no study has simultaneously compared the responsiveness of the most frequently used outcome measurements after PR. We designed this study to investigate the capacity of several of the most frequently used outcome measurements to detect changes after PR in a population of patients with severe COPD who qualified for lung volume reduction surgery. DESIGN, PATIENTS, AND INTERVENTIONS: We evaluated 37 patients with severe COPD (FEV(1) < 40%) before and after 6 to 8 weeks of outpatient PR. The following frequently used tools were evaluated: the 6-min walk distance (6MWD); functional dyspnea with the Medical Research Council (MRC) scale; baseline and transitional dyspnea index (BDI/TDI); resting and 6MWD visual analog scale (VAS); quality of life with a generic tool (the Short Form-36 [SF-36]); and two disease-specific tools, the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). RESULTS: After PR, mean +/- SD 6MWD increased in 33 of 37 patients (89%), from 285 +/- 97 to 343 +/- 92 m (p = 0.009). Improvements were seen also in the MRC scale in 23 of 37 patients (62%; from 2.27 +/- 0.8 to 1.86 +/- 0.6; p = 0.01); in CRQ dyspnea in 25 of 37 patients (67%; from 3.25 +/- 0.9 to 3.90 +/- 1.4; p = 0.02); in CRQ mastery in 22 of 37 patients (60%; from 4.37 +/- 1.4 to 5.14 +/- 1.3; p = 0.01); and in BDI/TDI functional in 24 of 37 patients (64%; from 1.4 +/- 0.8 to 0.7 +/- 1.1; p = 0.002). There were smaller improvements in the SGRQ in 18 of 37 patients (48%) and in the SF-36 in 19 of 37 patients (51%), but they were not statistically significant. There were good correlations between the dyspnea components of all the tools. The 6MWD change did not correlate with the changes in the other outcomes. Clinically significant changes in the values for those outcome tools were detected in > 50% of patients for the BDI/TDI, 29% of patients for the MRC scale, in 37% of patients for the 6MWD, in 48% of patients for the VAS at peak exercise, in > 50% of patients for the CRQ, and in 40% of patients for the SGRQ. CONCLUSIONS: We conclude that the VAS peak exercise, BDI/TDI, and CRQ adequately reflect the beneficial effects of PR. The 6MWD evaluates a unique domain not related to quality of life. Due to their simplicity and sensitivity, VAS at peak exercise, 6MWD, and CRQ may be the best practical tools to evaluate responsiveness to PR.

Aged↗