PubMed Health⌕ Search

Biomedical subjects

C F Donner

Publications and source records attributed to C F Donner.

At least 19 recordsLinked to original sources
PubMed2000

Influence of clinical history on airways bacterial colonization in subjects with chronic tracheostomy.

Patients with chronic tracheostomy are subject to significant bacterial colonization of the airways, a risk factor for respiratory infections. The aim of our study was to verify whether bacterial colonization and humoral immune response in the airways can be influenced by the disease which led to chronic respiratory failure and tracheostomy. Thirty-nine clinically stable outpatients with chronic tracheostomy were considered: 24 were affected by chronic obstructive pulmonary disease (COPD) (mean age 66 years, range 54-78, M/F 19/3; months since tracheostomy 23, range 3-62), 15 by restrictive lung disease (RLD) (12 thoracic wall deformities, three neuromuscular disease; age 57 years, range 41-72; M/F 3/12, months since tracheostomy 22, range 2-68). Recent antibiotic or corticosteroid treatments (< 1 month) were among exclusion criteria. Bacterial counts were assessed in tracheobronchial secretions with the method of serial dilutions. Identification of bacterial strains was performed by routine methods. Albumin, IgG, A, and M were measured in airways secretions with an immunoturbidimetric method. No significant differences were found between the two groups as regards either the quantitative bacterial cultures (RLD 81.4, 2.6-4200 x 10(4); COPD 75.9, 1.0-1530 x 10(4) colony forming units (cfu)/ml, geometric mean, range) or the prevalence of the main bacterial strains, (Pseudomonas species: 38 and 37%, Serratia marcescens: 31 and 23%, Staphylococcus aureus: 14 and 6%, Proteus species: 3 and 8%, for RLD and COPD respectively) as a percentage of total strains isolated (RLD = 26, COPD = 48). Immunoglobulin levels did not show significant differences, apart from being higher in underweight subjects. We conclude that in our series of stable outpatients with chronic tracheostomy, bacteria-host interaction in the airways was not influenced by the clinical history.

Adult↗
PubMed2000

Blood pressure and heart rate during periodic breathing while asleep at high altitude.

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.

Acclimatization↗
PubMed2000

Physiologic determinants of ventilator dependence in long-term mechanically ventilated patients.

To investigate the pathophysiologic mechanisms of ventilator dependence, we took physiologic measurements in 28 patients with COPD and 11 postcardiac surgery (PCS) patients receiving long-term mechanical ventilation during a spontaneous breathing trial, and in 20 stable, spontaneously breathing patients matched for age and disease. After 40 +/- 14 min of spontaneous breathing, 20 of 28 patients with COPD and all 11 PCS patients were judged ventilator-dependent (VD). We found that in the 31 VD patients tidal volume was low (VT: 0.36 +/- 0.12 and 0.31 +/- 0.08 L for COPD and PCS, respectively), neuromuscular drive was high (P(0.1): 5.6 +/- 1. 6 and 3.9 +/- 1.9 cm H(2)O), inspiratory muscle strength was reduced (Pdi(max): 42 +/- 12 and 28 +/- 15 cm H(2)O), and lung mechanics were abnormal, particularly PEEPi (5.9 +/- 3.0 cm H(2)O) and lung resistance (22.2 +/- 9.2 cm H(2)O/L/s) in COPD. The load/capacity balance was altered (Pdi/Pdi(max) and Ppl/Ppl(max) > 0.4) and the effective inspiratory impedance was high (P(0.1)/VT/TI >/= 10 cm H(2)O/L/s). Failure to wean occurred in patients with f/VT > 105 breaths/min/L and 56% of patients with COPD with f/VT < 80 breaths/min/L. Those who failed despite a low f/VT ( < 80 breaths/min/L) either showed ineffective inspiratory efforts, which artificially lowered f/ VT (n = 8), or did not increase breathing frequency (n = 5), but P(0.1) and P(0.1)/VT/TI were as high as in other VD patients. In the 31 VD patients, Pa(CO(2)) increased during the weaning trial (+12.3 +/- 8.0 mm Hg). We conclude that in the presence of a high drive to breathe, the imbalance between increased work load and reduced inspiratory muscle strength causes respiratory distress and CO(2) retention. Noninvasive measurements (breathing pattern, P(0.1), P(0.1)/ VT/TI) may give better insight into weaning failure useful in clinical decision-making, particularly in patients with COPD not showing rapid shallow breathing (56% in this study).

Aged↗
PubMed2000

Inhaled corticosteroids in stable COPD patients: do they have effects on cells and molecular mediators of airway inflammation?

STUDY OBJECTIVE: To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients. DESIGN: Six-week open preliminary prospective study. SETTING: A university respiratory disease clinic. PATIENTS: : Stable COPD patients with mild disease. INTERVENTION: Six-week treatment with inhaled beclomethasone (1.5 mg die). MEASUREMENTS: The levels of interleukin (IL)-8, myeloperoxidase, eosinophilic cationic protein and tryptase, and cell numbers in bronchial lavage specimens were determined, and the symptom score, the endoscopic bronchitis index, and functional parameters were recorded. RESULTS: After treatment there were significant reductions in the lavage levels of IL-8 ([mean +/- SEM] 1,603.4 +/- 331.2 vs 1,119.2 +/- 265.3 pg/mL, respectively; p = 0. 01) and myeloperoxidase (1,614.5 +/- 682.3 vs 511.2 +/- 144.2 microg/L, respectively; p = 0.05), in cell numbers (250.6 +/- 27.7 vs 186.3 +/- 11.5 cells x 10(3)/mL, respectively; p = 0.04), neutrophil proportion (59.7 +/- 14.3% vs 31.5 +/- 10.1%; p = 0.01), symptom score (4.5 +/- 0.6 vs 1.4 +/- 0.5; p = 0.01), and bronchitis index (8.5 +/- 0.8 vs 5.5 +/- 0.7; p = 0.007). CONCLUSIONS: In stable patients with COPD, inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation.

Administration, Inhalation↗
PubMed2000

Long-acting beta2 agonists in the management of stable chronic obstructive pulmonary disease.

Long-acting beta2 agonist bronchodilators (e.g. formoterol, salmeterol) are a new interesting therapeutic option for patients with chronic obstructive pulmonary disease (COPD). In the short term, both salmeterol and formoterol appear to be more effective than short-acting beta2 agonists, and in patients with stable COPD they are more effective than anticholinergic agents and theophylline. Regular treatment of patients with COPD with long-acting beta2 agonists can induce an improvement in the respiratory function and certain aspects of quality of life. Moreover, salmeterol seems to be better than ipratropium and theophylline in improving lung function at the recommended doses after a long term treatment. Use of combination therapy of a long-acting inhaled beta2 agonist and an anticholinergic agent or theophylline in patients with COPD has not been sufficiently studied. Combination of usual doses of ipratropium or oxitropium with usual doses of salmeterol or formoterol does not appear to improve pulmonary function, but this lack of improvement with the combination should not, in itself, prevent implementation of further therapeutic steps in patients responsive to an anticholinergic agent and/or salmeterol or formoterol administered singly. Neither formoterol nor salmeterol elicit significant cardiovascular effects in healthy individuals and patients with reversible airway obstruction. However, adverse cardiac events might occur in patients with COPD with pre-existing cardiac arrhythmias and hypoxaemia if they use long-acting 12 agonists, although the recommended single dose of salmeterol 50 microg or formoterol 12 microg ensures a relatively higher safety margin than formoterol 24 microg. The bronchodilatory effect of long-acting beta2 agonists seems to be fairly stable after regular treatment with these bronchodilators. Moreover, pre-treatment with a conventional dose of formoterol or salmeterol does not preclude the possibility of inducing further bronchodilation with salbutamol in patients with partially reversible COPD. All these findings support the use of long-acting beta2 agonist bronchodilators as first-line bronchodilator therapy for the long term treatment of airflow obstruction in patients with COPD. However, since physicians must always choose a drug that is highly efficacious, well tolerated and inexpensive, the cost-effectiveness analysis in relation to other bronchodilators will determine the proper place of long-acting beta2 agonists in the long term therapy of stable COPD.

Adrenergic beta-2 Receptor Agonists↗
PubMed1999

Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.

BACKGROUND: Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in patients with chronic heart failure (CHF), and it may be associated with sympathetic activation. The aim of the present study was to evaluate whether CSR could affect prognosis in patients with CHF. METHODS AND RESULTS: Sixty-two CHF patients with left ventricular ejection fraction </=35%, in NYHA class II to III, underwent clinical evaluation, Doppler echocardiography, ergospirometry, phenylephrine test, Holter recording, and a sleep study to evaluate the occurrence of CSR, expressed as percentage of periodic breathing, and apnea/hypopnea index (AHI) (ie, the number of apneas and hypopneas per hour of recording). During a mean follow-up of 28+/-13 months, 15 patients died of cardiac causes. Nonsurvivors were in a higher NYHA functional class than survivors (P<0.001) and had a more depressed left ventricular ejection fraction (P<0.03), a shorter deceleration time of early filling (P<0. 05), larger left and right atria (P<0.05 and P<0.02, respectively) and a lower peak V(O2) (P<0.05). Nonsurvivors also spent a greater percentage of the night in periodic breathing (P<0.01) with a greater AHI (P<0.03) and showed lower values of diurnal baroreflex sensitivity (P<0.05) and of heart rate variability (sdNN: P<0.01). Multivariate analysis revealed the AHI (chi2, 10.4; P<0.01), followed by left atrial area (chi2, 5.7; P<0.01), as the only independent and additional predictors of subsequent cardiac death. Patients at very high risk for fatal outcome could be identified by an AHI >/=30/h and left atria >/=25 cm2. CONCLUSIONS: The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI >/=30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.

Aged↗
PubMed1999

Oral bambuterol compared to inhaled salmeterol in patients with partially reversible chronic obstructive pulmonary disease.

OBJECTIVE: There is now good evidence that inhaled salmeterol is an effective agent in chronic obstructive pulmonary disease (COPD),but, at the present time, data on the effects of bambuterol, which is an oral tarbutaline pro-drug, in patients with COPD are scarce. Moreover, no comparative study between bambuterol and salmeterol in patients with chronic obstructive airway disorders has been published. The objective of this research was, consequently, to compare the efficacy and safety of 20 mg oral bambuterol and 50 microg inhaled salmeterol in patients with partially reversible COPD. METHODS: The speed and length of bronchodilation with 20 mg bambuterol and 50 microg inhaled salmeterol were compared in 16 patients with partially reversible COPD. The investigation and designed as a double-blind, double-dummy, cross-over, placebo controlled and randomised study. Lung function (FEV1, FVC) and systemic variables (subjective tremor, heart rate, blood pressure) were monitored prior to the administration of the drug and for 12 h after each agent on 3 non-consecutive days. RESULTS: Inhalation of salmeterol induced a significant (P < 0.05) increase of lung function when compared with placebo. In addition, oral bambuterol elicited good bronchodilation, with its maximum slightly later than for salmeterol. The mean (+/- SE) AUC(0-12h)S for all patients were 3.134 1 +/- 0.553 for salmeterol and 1963 1 +/- 0.573 for bambuterol. Both AUC(0-12h)S were significantly greater than for placebo (P < 0.05), but there was no significant difference (P = 0.077) between the salmeterol and bambuterol AUC(0-12h)S. Bambuterol, but not salmeterol, caused tremor in four patients. Moreover, it induced a higher heart rate when compared with salmeterol at each considered time after the administration of the drug; differences after 9 and 12 h were statistically significant (P < 0.05). CONCLUSION: Both oral bambuterol and inhaled salmeterol resulted in good bronchodilation in patients with stable COPD. However, bambuterol, but not salmeterol, caused tremor in several subjects and elicited a more pronounced tachycardia.

Administration, Inhalation↗
PubMed1999

Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics.

CC-chemokines are chemotactic factors expressed in a wide range of cell types and tissues. The aim of this study was to evaluate the involvement of CC-chemokines in the airways inflammation of patients affected by chronic bronchitis. The study evaluated, with an immunoassay, the concentrations of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta), in the bronchoalveolar lavage fluid (BALF) of 12 smokers affected by chronic bronchitis and 14 smoking, 15 nonsmoking and six exsmoking healthy subjects. MCP-1 was significantly increased in patients with chronic bronchitis ((mean+/-SD) 10.75+/-4.04 pg x mL(-1)) and in the smoker control group (12.39+/-5.87 pg x mL(-1)) compared with healthy exsmokers: (7.12+/-1.60 pg x mL(-1), p=0.035 and p=0.045, respectively) and nonsmokers (6.41+/-3.87 pg x mL(-1), p=0.003 and p=0.006, respectively). MIP-1alpha concentrations were undetectable. A significant difference was observed in MIP-1-beta levels in BALF of chronic bronchitics (8.11+/-5.97 pg x mL(-1)) compared to smoker (3.57+/-2.90 pg x mL(-1), p=0.018), exsmoker (3.43+/-0.68 pg x mL(-1), p=0.025) and nonsmoker (3.39+/-3.73 pg x mL(-1), p=0.008) control groups. A negative correlation was observed between MIP-1beta levels and forced expiratory volume in one second values (p=-0.64, p=0.035) in chronic bronchitics. An increase of monocyte chemotactic protein-1 is related to smoking habit and seems consistent with a lung inflammatory reaction. On the contrary, an increase in macrophage inflammatory protein-1beta levels is restricted to smokers developing chronic obstructive pulmonary disease. These data suggest a role of CC-chemokines in the pathogenesis of chronic bronchitis.

Biomarkers↗
PubMed1999

Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium bromide at the clinically recommended dose (40 microg) does not produce any further bronchodilation than that achieved with salmeterol 50 microg alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS: Thirty two outpatients received 50 microg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled oxitropium bromide (100 microg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs-that is, a total cumulative dose of 600 microg oxitropium bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 microg salmeterol + 600 microg oxitropium bromide; (2) 50 microg salmeterol + placebo; (3) placebo + 600 microg oxitropium bromide; (4) placebo + placebo. RESULTS: Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV(1)) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS: This study shows that acute pretreatment with 50 microg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

Administration, Inhalation↗
PubMed1999

Physiologic response of ventilator-dependent patients with chronic obstructive pulmonary disease to proportional assist ventilation and continuous positive airway pressure.

To investigate the physiologic effects of proportional assist ventilation (PAV) in difficult-to-wean, mechanically ventilated patients with advanced COPD, we measured in eight ICU patients the breathing pattern, neuromuscular drive (P0.1), lung mechanics, and inspiratory muscle effort (PTPdi and PTPpl) during both spontaneous breathing (SB) and ventilatory support with PAV, CPAP, and CPAP + PAV (in random sequence). PAV (volume assist [VA] and flow assist [FA]) was set as follows: dynamic lung elastance and inspiratory pulmonary resistance were measured during SB; then VA and FA were set to counterbalance the elastic and resistive loads exceeding the normal values, respectively, the inspiratory muscles bearing a normal elastic and resistive workload. CPAP was set close to dynamic intrinsic PEEP (8.3 +/- 3.4 cm H2O). We found significant reductions in P0.1 and PTPdi during both CPAP (-45 and -37%, respectively) and PAV (-50 and -48%, respectively). However, only the combination of PAV and CPAP brought P0.1 (1.69 +/- 0.97 cm H2O) and PTPdi (100 +/- 68 cm H2O. s) within normal values, and ameliorated the breathing pattern compared with SB (tidal volume: 0.69 +/- 0.33 versus 0.33 +/- 0.14 L; breathing frequency, 14.6 +/- 4.6 versus 21.0 +/- 6.5 breaths/min, respectively), without generating ineffective inspiratory efforts. We conclude that in difficult-to-wean COPD patients, (1) PAV improves ventilation and reduces both P0.1 and inspiratory muscle effort; (2) the combination of PAV and CPAP can unload the inspiratory muscles to values close to those found in normal subjects.

Aged↗
PubMed1999

Analysis of factors that characterize health impairment in patients with chronic respiratory failure. Quality of Life in Chronic Respiratory Failure Group.

This study was designed to identify a core set of items that may characterize impaired health in chronic respiratory failure (CRF) since none of the questionnaires commonly used to measure impaired health in patients with CRF were developed for use in such patients. Questionnaire items, identified from several sources, were administered to 92 patients with stable severe chronic hypoxia or hypercapnia, together with physiological measures of disease severity, the Sickness Impact Profile (SIP) and the St George's Respiratory Questionnaire (SGRQ). Of the 152 items identified, only 28 correlated with patients' perceptions of overall health and were also independent of age, sex, disease or type of treatment and did not show floor or ceiling effects. Principal components analysis identified three specific factors: "daily activities", "cognitive function", and "invalidity". The total score for the whole 28-item set correlated with other measures of disease activity, including SGRQ (r = 0.86) and SIP (r = 0.70), but not spirometry. The interquartile range of the 28-item set was wider than that of the SGRQ or the SIP. This study characterized two areas of health impairment in chronic respiratory failure that had not previously been identified: effects of impaired cognitive function on daily life, and a sense of invalidity. The measurements properties of this 28-item set suggest that it may be a more discriminative instrument for patients with chronic respiratory failure than existing questionnaires.

Activities of Daily Living↗
PubMed1999

Infectious exacerbations of chronic bronchitis. ORIONE Board.

Approximately 50% of chronic bronchitis exacerbations are caused by bacteria and 25-50% by viruses. Streptococcus pneumoniae and Haemophilus influenzae are traditionally considered leading pathogens. In Italy, S. pneumoniae and H. influenzae resistance to beta-lactams is low but resistance to macrolides is more widespread. Pathogenic bacteria are isolated in the airways of most chronic bronchitis patients, impairing host respiratory defences, further predisposing towards infection and, thus, establishing a vicious circle, fuelled by damage due to cigarette smoking. The diagnosis of an exacerbation is essentially clinical. Lung function testing may show no modification, or indicate worsening airway obstruction. Blood gas analysis is performed in severe cases. The utility of culture is lessened by evidence of airway bacterial contamination in clinically stable periods. Quantitative thresholds have been identified over and above which bacterial exacerbation is considered probable. General preventative measures include the adoption of hygiene-behavioural standards. Antibiotic prophylaxis is not advisable. Prophylaxis by means of vaccination is indicated against influenza. Vaccination against S. pneumoniae is available but is seldom employed. The principal form of treatment is antibiotic therapy, but there is an ongoing debate regarding the objective criteria for its use. A recent meta-analysis showed a small but statistically significant difference in favour of antibiotic treatment. The antibiotic cost-benefit ratio is favourable in patients with severe functional impairment. Oral administration is to be preferred as more practical and less costly for equal efficacy. In selecting an antibiotic, pharmacokinetic considerations (bioavailability, tissue diffusion, half-life) must be kept in mind. Prescription should be oriented towards drugs active against the most commonly occurring pathogens. In more severe cases coverage against Gram-negative bacteria is considered. Complementary medical treatment includes bronchodilators corticosteroids, diuretics, and oxygen therapy. Chest physiotherapy may be beneficial. Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode. In a high number of cases endotracheal intubation may be avoided. Most exacerbations may be treated on an outpatient basis, but in some cases admission to hospital is indicated.

Acute Disease↗
PubMed1999

Asthma controller therapy: role of antileukotrienes, a new therapeutic class.

Asthma is a chronic disease and should be treated with both controller and reliever drugs. Asthma controller therapy is not used sufficiently widely, probably due to low compliance with inhaled drugs, lack of response in some patients to low-medium doses of inhaled steroids and possible adverse events. This review analyses a new class of antiasthmatic drugs, leukotriene receptor antagonists (antileukotrienes). At present, two antileukotrienes are available in Italy: zafirlukast and montelukast. Antileukotrienes improve symptoms and also inhibit the effects of some of the inflammatory mediators involved in the pathogenesis of asthma; therefore, antileukotrienes may be used in monotherapy. In addition, the oral administration route is an advantage for compliance. Antileukotrienes significantly improve pulmonary function, asthma symptoms and inhaled and oral steroid and short-acting beta 2-agonist use. Moreover, antileukotrienes produce a 50% mean reduction in the incidence of asthma exacerbations compared with placebo. From the economic point of view, asthma controller therapy using antileukotrienes is associated with a > 50% (compared with placebo) reduction in healthcare costs (hospitalization due to asthma exacerbation, healthcare contact and absenteeism from work or school), which globally account for 93% of asthma-related costs. Antileukotrienes are indicated in the treatment of persistent mild-to-severe asthma, seasonal allergic asthma, exercise-induced asthma and aspirin-induced asthma. Antileukotrienes are well tolerated independently of the duration of treatment and the incidence of the observed adverse events is substantially similar to that observed using placebo. Owing to good tolerability and compliance and the economic advantages, these agents may be considered a valid therapeutic option for the control and management of asthma as a chronic disease.

Administration, Inhalation↗
PubMed1998

Static intrinsic PEEP in COPD patients during spontaneous breathing.

Intrinsic positive end-expiratory pressure (PEEPi) is routinely determined under static conditions by occluding the airway at end-expiration (PEEPi,st). This procedure may be difficult in patients with chronic obstructive pulmonary disease (COPD) during spontaneous breathing, as both expiratory muscle activity and increased respiratory frequency often occur. To overcome these problems, we tested the hypothesis that the difference between maximum airway opening (MIP) and maximum esophageal (Ppl max) pressures, obtained with a Mueller maneuver from the end-expiratory lung volume (EELV), can accurately measure PEEPi,st. Using this method, we found that, in eight ventilator-dependent tracheostomized COPD patients (age 71+/-7 yr), PEEPi,st averaged 13.0+/-2.9 cm H2O. That measurement was validated by comparison with a reference static PEEPi (PEEPi,st-Ref) taken at the same EELV adopted by patients during spontaneous breathing, and measured on the passive quasi-static pressure-volume (P/V) curve of the respiratory system, obtained during mechanical ventilation. PEEPi,st-Ref averaged 13.1+/-3.0 cm H2O, i.e., a value essentially equal to PEEPi,st measured by means of our technique. We conclude that PEEPi,st can be accurately assessed in spontaneous breathing COPD patients by the difference between MIP and Ppl max during the Mueller maneuver.

Aged↗
PubMed1998

Severity of airflow limitation is associated with severity of airway inflammation in smokers.

To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1alpha+ epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0. 012), NK-lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of MIP-1alpha+ epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the bronchial mucosa.

Aged↗
PubMed1998

Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease.

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Effects of high-altitude periodic breathing on sleep and arterial oxyhaemoglobin saturation.

This study aimed to investigate the effect of periodic breathing (PB) at high altitude on sleep structure and arterial oxygen saturation (Sa,O2). Five healthy subjects underwent polysomnographic studies at sea level, and during the first and the fourth week of sojourn at 5,050 m. Their breathing pattern, sleep architecture and Sa,O2 were analysed. PB was detected in the high-altitude studies during nonrapid eye movement (NREM) sleep and tended to increase from the first to the fourth week. Stages 3-4 were absent in four subjects at the first week, but only in one at the fourth week, irrespective of the amount of PB. The arousal index was 11.6+/-3.8 at sea level, 30.1+/-15.5 at the first week at altitude and 33.0+/-18.2 at the fourth week. At altitude, arousal index in NREM sleep was higher during PB than during regular breathing. In NREM sleep, the mean highest Sa,O2 levels in NREM epochs with PB were higher than in those with regular breathing by 2.8+/-1.7% at the first week and 2.9+/-1.5% at the fourth week (p<0.025). From the first to the fourth week, mean Sa,O2 increased significantly during wakefulness (5.6%), NREM (5.2% with regular breathing and 5.3% with PB) and rapid eye movement sleep (7.6%). The data demonstrate a slight role of periodic breathing in altering sleep architecture at high altitude and also show that periodic breathing induces only a minor improvement in arterial oxygen saturation during nonrapid eye movement sleep.

Acclimatization↗