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Biomedical subjects

Claudio F Donner

Publications and source records attributed to Claudio F Donner.

16 recordsLinked to original sources
PubMed2006

Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.

BACKGROUND: The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHOD: An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory volume in 1 second [FEV(1)]: 53 +/- 19% [mean +/- SD]) patients with a history of smoking (53 +/- 34 pack/years) and in 10 patients with adenocarcinoma or adenosquamous carcinoma (ASC). Immunopositivity was quantified in the bronchial epithelium and in specimens with ASC. RESULTS.: In smokers with COPD, 10 out of 35 patients had a normal bronchial epithelium (NBE), 12 showed basal cell hyperplasia (BCH), 5 squamous metaplasia (SM), and 8 dysplasia (Dy). It was found that 58 +/- 23% and 54 +/- 23% of NBE and 48 +/- 29% and 52 +/- 26% of BCH expressed Hsp60 and Hsp10, respectively; in contrast, only 3 +/- 3% and 3.6 +/- 2% of SM, 1.9 +/- 4% and 1.1 +/- 2% of Dy expressed Hsp60 and Hsp10, respectively. ASC specimens were negative for Hsps proteins. Interestingly, NBE also present at the edges of ASC specimens was negative for Hsps proteins. CONCLUSIONS: The loss of Hsp60 and Hsp10 immunopositivity is related to the development and progression of bronchial cancer in smokers with COPD.

Adenocarcinoma↗
PubMed2006

A randomized controlled trial on office spirometry in asthma and COPD in standard general practice: data from spirometry in Asthma and COPD: a comparative evaluation Italian study.

STUDY OBJECTIVES: To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. METHODS: A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged 18 to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Rome, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. RESULTS: Seventy-four GPs complied to the trial. Of 333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). CONCLUSIONS: Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.

Adult↗
PubMed2005

Acute exacerbation of chronic bronchitis: need for an evidence-based approach.

Acute exacerbations of chronic bronchitis (AECB) can be classified into three levels according to severity: (1) home treatment sufficient; (2) hospitalisation required; (3) hospitalisation in the presence of respiratory failure. This evidence-based classification is useful in ranking the clinical relevance of the episode and its outcome, and makes it possible to define the clinical history, clinical evaluation and diagnostic procedures of an exacerbation. Treatment guidelines vary according to severity, but they are essentially based on appropriate bronchodilator therapy (beta(2) agonists and/or anticholinergics, corticosteroids and antibiotics selected according to the local bacterial resistance pattern). It is important that cases requiring management in an intermediate/special respiratory care unit or intensive care unit (ICU) be identified. This is the stage where oxygen therapy and ventilatory support become particularly important. As first choice, they should be non-invasive, saving intubation and invasive ventilatory support for most severe cases characterised by severe acidemia and hypercapnia. We identify the optimal criteria for hospital discharge and follow-up of patients with AECB. In view of the chronic nature of the underlying disease, a correct follow-up is essential to avoid frequent and repeated relapses.

Bronchitis, Chronic↗
PubMed2005

Noninvasive proportional assist ventilation and pressure support ventilation during arm elevation in patients with chronic respiratory failure. A preliminary, physiologic study.

BACKGROUND: It has been shown that upper limbs activity increases the respiratory workload in patients with chronic respiratory failure (CRF). The object of the present study was to investigate whether, in these patients: (i) noninvasive positive pressure ventilation (NPPV) could sustain the inspiratory muscles to meet the greater ventilatory demand during upper limbs activity with the arm elevation test (AE); (ii) proportional assist ventilation (PAV) might be superior to pressure support ventilation (PSV) during AE, because of its potential more adaptable response to sudden changes in the ventilatory pattern. METHODS: The study was performed in the pulmonary function laboratory of the Pulmonary Division in Verona General Hospital, Verona, Italy. We studied 8 male patients with CRF due to chronic obstructive pulmonary disease (COPD). Each patient received 2 treatment in random order with a crossover design: spontaneous breathing (SB), SB with AE, either PSV or PAV without and with AE, SB without and with AE, either PSV or PAV without and with AE. We measured: lung function tests, lung mechanics, ventilatory pattern and diaphragmatic effort (pressure time product, PTP(di)). RESULTS: (i) AE increases minute ventilation (+14%) and PTP(di) (+64%); (ii) ventilatory support, both with PSV and PAV unloads the diaphragm both at rest (PTP(di) -77% and -54%, respectively) and during arm elevation (PTP(di) -54% and -44%, respectively). CONCLUSIONS: PAV and PSV unloads the diaphragm in patients with CRF due to COPD both during SB and AE; PAV can be more efficient than PSV in assisting the diaphragm during AE in producing a greater level of minute ventilation for a similar rise in PTP(di) compared to PSV. Noninvasive ventilatory support should be considered in rehabilitation programs for training of upper limbs activity.

Aged↗
PubMed2005

Treatments for COPD.

The multicomponent nature of chronic obstructive pulmonary disease (COPD) has provided a challenging environment in which to develop successful treatments. A combination of pharmacological and non-pharmacological approaches is used to combat this problem, and an overview of these approaches and their possible future direction is given. Bronchodilators are the mainstay of COPD treatment and can be combined with inhaled corticosteroids for greater efficacy and fewer side effects. A new generation of pharmacotherapeutic agents, most notably phosphodiesterase-4 inhibitors, which are already in the advanced stages of clinical development, and leukotriene B4 inhibitors (in early clinical development), may shape future treatment as further insight is gained into the pathological mechanisms underlying COPD. Non-pharmacologic treatments for COPD include long-term oxygen therapy (LTOT), nasal positive pressure ventilation (nPPV), pulmonary rehabilitation and lung-volume-reduction surgery (LVRS). Apart from smoking cessation, LTOT is the only treatment to date which has been shown to modify survival rates in severe cases; thus its role in COPD is well defined. The roles of nPPV and LVRS are less clear, though recent progress is reported here. In the future, it will be important to establish the precise value of the different treatments available for COPD--evaluating both clinical and physiological endpoints and using the data to more accurately define candidate patients accordingly. The challenge will be to develop this base of knowledge in order to shape future research and allow clinicians to deliver tailored COPD management programmes for the growing number of patients afflicted with this disease.

Bronchodilator Agents↗
PubMed2005

Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease.

BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.

Aged↗
PubMed2005

Effectiveness of mask and helmet interfaces to deliver noninvasive ventilation in a human model of resistive breathing.

The helmet, a transparent latex-free polyvinyl chloride cylinder linked by a metallic ring to a soft collar that seals the helmet around the neck, has been recently proposed as an effective alternative to conventional face mask to deliver pressure support ventilation (PSV) during noninvasive ventilation in patients with acute respiratory failure. We tested the hypothesis that mechanical characteristics of the helmet (large internal volume and high compliance) might impair patient-ventilator interactions compared with standard face mask. Breathing pattern, CO(2) clearance, indexes of inspiratory muscle effort and patient-ventilator asynchrony, and dyspnea were measured at different levels of PSV delivered by face mask and helmet in six healthy volunteers before (load-off) and after (load-on) application of a linear resistor. During load-off, no differences in breathing pattern and inspiratory muscle effort were found. During load-on, the use of helmet to deliver pressure support increased inspiratory muscle effort and patient-ventilator asynchrony, worsened CO(2) clearance, and increased dyspnea compared with standard face mask. Autocycled breaths accounted for 12 and 25% of the total minute ventilation and for 10 and 23% of the total inspiratory muscle effort during mask and helmet PSV, respectively. We conclude that PSV delivered by helmet interface is less effective in unloading inspiratory muscles compared with PSV delivered by standard face mask. Other ventilatory assist modes should be tested to exploit to the most the potential benefits offered by the helmet.

Adult↗
PubMed2005

Inhaled beta2-adrenoceptor agonists: cardiovascular safety in patients with obstructive lung disease.

Although large surveys have documented the favourable safety profile of beta(2)-adrenoceptor agonists (beta(2)-agonists) and, above all, that of the long-acting agents, the presence in the literature of reports of adverse cardiovascular events in patients with obstructive airway disease must induce physicians to consider this eventuality. The coexistence of beta(1)- and beta(2)-adrenoceptors in the heart clearly indicates that beta(2)-agonists do have some effect on the heart, even when they are highly selective. It should also be taken into account that the beta(2)-agonists utilised in clinical practice have differing selectivities and potencies. beta(2)-agonist use has, in effect, been associated with an increased risk of myocardial infarction, congestive heart failure, cardiac arrest and sudden cardiac death. Moreover, patients who have either asthma or chronic obstructive pulmonary disease may be at increased risk of cardiovascular complications because these diseases amplify the impact of these agents on the heart and, unfortunately, are a confounding factor when the impact of beta(2)-agonists on the heart is evaluated. Whatever the case may be, this effect is of particular concern for those patients with underlying cardiac conditions. Therefore, beta(2)-agonists must always be used with caution in patients with cardiopathies because these agents may precipitate the concomitant cardiac disease.

Administration, Inhalation↗
PubMed2004

Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD.

Oxidative stress caused by airway inflammation is increased in chronic obstructive pulmonary disease (COPD) and may account for the progressive deterioration of structure and function of the respiratory tract observed in this disease. Antioxidant defences of the respiratory tract may be overwhelmed by the oxidant burden in COPD and possibly restored with antioxidant therapy. The level of hydrogen peroxide (H(2)O(2)) concentration in exhaled air condensate (EAC) is a valuable tool for assessing and monitoring oxidative stress. This study aimed to verify the effect of 2-month oral N-acetylcysteine (NAC) treatment compared to placebo on the H(2)O(2) content in EAC of 55 clinically stable COPD patients (48 males), mean age 65.93+/-9.3 years. After clinical examination, pulmonary function tests, and collection of EAC for the basal (T0) assay of H(2)O(2), patients were randomly allocated to group A (usual therapy plus oral NAC 600 mg b.i.d. for 2 months) or group B (usual therapy plus placebo b.i.d. for 2 months). H(2)O(2) assay in EAC was repeated at 15 (T15), 30 (T30), and 60 (T60) days after the start of therapy in each group. All patients were non-smokers or ex smokers for at least 5 years and the two groups were comparable in terms of demographic, respiratory function, and EAC data at baseline. The H(2)O(2) level in EAC of group A was significantly decreased at T15 (1.00+/-0.38 SD microM; p=0.003), T30 (0.91+/-0.44 microM; p=0.007), and T60 (0.83+/-0.41 microM; p=0.000) compared to T0 (1.28+/-0.61 microM). No significant decrease in H(2)O(2) of group B was found at any time point. We conclude that oral NAC 600 mg b.i.d. for 2 months rapidly reduces the oxidant burden in airways of stable COPD patients.

Acetylcysteine↗
PubMed2003

MVarallo: a new M(Like) alpha 1-antitrypsin-deficient allele.

A 73-year-old never-smoker woman with chronic bronchitis, increasing dyspnoea, and airflow limitation with a FEV1 of 49% of predicted value had low serum level of alpha-1-antitrypsin (69 mg/dL, normal range 150-350). Isoelectric focusing showed an Mlike pattern. Direct sequencing showed, in the second exon, a particular DNA alteration localized between codon 41 and codon 51: a region of 30 base pairs (bp) was completely deleted and substituted by a 22-bp sequence. The resulting loss of 8 bp yields, in the second exon, a 70-71 stop codon. This new Mlike variant was denominated MVarallo from the site where it was discovered.

Aged↗
PubMed2002

Increased macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta levels in bronchoalveolar lavage fluid of patients affected by different stages of pulmonary sarcoidosis.

Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta are two CC chemokines that induce lymphocyte migration. MIP-1alpha preferentially mediates chemotaxis of CD8 rather than CD4 lymphocytes, whereas the reverse is true for MIP-1beta. Both these chemokines recognize CCR5 as a cellular receptor in T lymphocytes and alveolar macrophages. We measured the concentrations of MIP-1alpha and MIP-1beta in bronchoalveolar lavage fluid (BALF) of 30 subjects affected by different stages of pulmonary sarcoidosis and 18 healthy normal subjects. We also evaluated the expression of CCR5 in alveolar macrophages and lymphocytes. The BALF concentrations of MIP-1alpha were significantly increased only in Stage II and III sarcoidosis. On the contrary, the concentrations of MIP-1beta were significantly increased at all stages. A striking increase of CCR5 expression was observed in both lymphocytes and macrophages of all patients, along with a trend to decreased positivity from Stage I to III of the disease. The MIP-1beta concentrations correlated with the number of total (r = 0.65, p = 0.0001) and both CD4 (r = 0.64, p = 0.0001) and CD8 (r = 0.62, p = 0.0001) lymphocytes; on the contrary, the MIP-1alpha concentrations correlated only with CD8 lymphocytes (r = 0.45, p = 0.002). Finally, significant negative correlations were observed between the neutrophil percentage and CCR5 expression in alveolar macrophages (r = -0.53, p = 0.005) and lymphocytes (r = -0.43, p = 0.01). Our results help to explain the mechanism of CD4 and CD8 recruitment and the possible involvement of CC chemokines in the fibrotic progression of sarcoidosis.

Adult↗
PubMed2002

Quality of life and long-term ventilation.

The interest in measuring HS or QoL in patients with respiratory diseases has increased progressively over the last decade, but only recently has it been applied to patients with more severe disease (ie, patients with CRF who are receiving LTOT or NIPPV). The impact of CRF on the daily life and well being of patients can be measured in a number of different ways. There is evidence, however, that it is not possible to predict patients' health from surrogate measures (eg, spirometry or exercise performance) and that the size of the health gain following treatments or interventions cannot be predicted from changes in physiologic measurements. Adequate assessments of HS can be measured directly only through the use of valid and reliable QoL questionnaires. A range of different instruments is available in the literature. The SGRQ and MRF28 have been shown to be applicable and reliable in patients on long-term ventilation.

Activities of Daily Living↗
PubMed2002

Mask proportional assist vs pressure support ventilation in patients in clinically stable condition with chronic ventilatory failure.

OBJECTIVE: To compare the short-term physiologic effects of mask pressure support ventilation (PSV) and proportional assist ventilation (PAV) in patients in clinically stable condition with chronic ventilatory failure (CVF). DESIGN: Randomized, controlled physiologic study. SETTING: Lung function units of two pulmonary rehabilitation centers. PATIENTS: Eighteen patients with CVF caused by COPD (11 patients) and restrictive chest wall diseases (RCWDs) [7 patients]. METHODS: Assessment of breathing pattern and minute ventilation (E), respiratory muscles and lung mechanics, and patient/ventilator interaction during both unassisted and assisted ventilation. After baseline assessment during spontaneous breathing (SB), mask PSV and PAV were randomly applied at the patient's comfort, with the addition of the same level of continuous positive airway pressure (2 cm H2O or 4 cm H2O in all patients), for 30 min each, with a 20-min interval of SB between periods of assisted ventilation. RESULTS: A longer time was spent to set PAV than PSV (663 +/- 179 s and 246 +/- 58 s, respectively; p < 0.001). Mean airway opening pressure (Pao) computed over a period of 1 min, but not peak Pao, was significantly lower with PAV than with PSV (151 +/- 45 cm H2O/s/min and 207 +/- 73 cm H2O/s/min, respectively; p < 0.002). Tidal volume (VT) exhibited a greater variability with PAV than with PSV (variation coefficient, 16.3% +/- 10.5% vs 11.6% +/- 7.7%, respectively; p < 0.05). Compared with SB, both modalities resulted in a significant increase in VT (by 40% and 36% with PAV and PSV, respectively, on average) and E (by 37% and 35%) with unchanged breathing frequency and duty cycle. Both modalities significantly reduced esophageal (by 39% and 51%) and diaphragmatic (by 42% and 63%) pressure-time products, respectively. Ineffective efforts were observed with neither modes of assistance in any patient. CONCLUSIONS: In resting, awake patients in clinically stable condition with CVF caused by either COPD or RCWD, noninvasive application of PAV, set at the patient's comfort, was not superior to PSV either in increasing VT and E or in unloading the inspiratory muscles. We failed to find any difference in patient/ventilator interaction between ventilatory modes.

Aged↗