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Biomedical subjects

C F Donner

Publications and source records attributed to C F Donner.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1998

The influence of personal tobacco smoking on the clinical practice of Italian chest physicians.

Tobacco smoking (TS) is a major cause of lung diseases. This study aimed to determine: 1) the prevalence of TS among chest physicians; 2) the influence of the personal smoking habit on clinical practice; and 3) what training about tobacco-related issues (TI) doctors received in medical school. A total of 983 attendees at the National Meeting of the Italian National Thoracic Society (AIPO) received a questionnaire about TI, which also contained the Fagerstroem Tolerance Questionnaire, and 605 (61.5%) answered. An independent assessment of the prevalence of smokers was carried out to minimize the bias of self-selection. The numbers of smokers was 151 (25%), never-smokers 246 (40.7%) and exsmokers 208 (34.4%). Smoking chest physicians underestimate the health hazards of smoking (p<0.001) and disregard their educational role (p=0.005) more than nonsmoking chest physicians. Compliance with smoking restrictions inside hospitals is frequently poor (30.1% smoke in clinics). In 33.1% of smokers a high nicotine addiction was found, which influenced their behaviour in hospital but not their ability to cope with tobacco-related problems. This ability was generally low: 39.1% of responders reported no training about TI. Smoking is frequent among Italian chest physicians, who are poorly trained about the health effects of tobacco smoking and are poorly skilled in treating smokers.

Adult↗
PubMed1998

Personal smoking habit and attitude toward smoking among the health staff of a general hospital.

Tobacco smoke (TS) is the single most important cause of preventable death in industrialized countries. Health staff have great responsibility in its control, but the smoking habits of health staff may influence their attitude toward patients. The aim of the study was to evaluate: 1) the prevalence of smoking among health staff at different professional levels; 2) the knowledge of smoking-related damage; and 3) how personal smoking habits influence behaviour in the workplace. A questionnaire was sent to all health staff of the Morelli Hospital (Sondalo, Italy) asking information about age, activity, smoking habits and attitude toward smoking: the Fagerstrom test was also administered to smokers. A total of 959 valid questionnaires were collected (57% of the whole sample). Results were analyzed by means of Chi-squared and Student t-tests, where appropriate. The prevalence of smokers was 44% former smokers 24% and lifetime nonsmokers 32%. The highest prevalence of TS was found in nursing students and auxiliaries (47%) and the lowest among doctors (39%). A clear cohort-effect due to age was evidenced: the youngest age-group (< 30 yrs old) presents the highest prevalence of lifetime nonsmokers and of light smokers, and the lowest of heavy smokers; the oldest age-group (> 40 yrs old) presents the highest prevalence of quitters and of heavy smokers, and the lowest of smokers and lifetime nonsmokers; the intermediate age-group (31-40 yrs old) presents the highest prevalence of smokers. The knowledge of smoking-related damage was poor, with significant differences between smokers and nonsmokers and the different professional categories. Tobacco smoking proved to be common behaviour (even when on duty) among health staff. A minority of health staff seem fully aware of personal and social smoking related aspects. Smoking habits influence the attitude of health staff toward patient counselling about tobacco smoking.

Adult↗
PubMed1997

Nocturnal asthma: mechanisms and therapy.

Nocturnal worsening of symptoms affects a large number of patients suffering from asthma. Recent studies show that airway inflammation underlies nocturnal awakenings and increased airway hyperreactivity. These studies, however, yield conflicting results concerning the pathogenesis of the disease, making it difficult to understand the mechanisms involved in sustaining nocturnal asthma. This article reviews the principal pathogenetic mechanisms of nocturnal asthma, showing that worsening of symptoms at night may be the result of a more severe disease as well as of increased inflammation at night and higher susceptibility. We also review the pharmacologic treatment of nocturnal asthma which is mainly based on antiinflammatory treatment with inhaled or oral steroids or combined therapies with theophylline and beta 2 agonists. The activity of antileukotrine compounds in asthma is also summarized.

Anti-Asthmatic Agents↗
PubMed1997

Lung alkaline phosphatase as a marker of fibrosis in chronic interstitial disorders.

Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and type II cell proliferation. Type II pneumocytes are extensively involved in fibrosis. The aim of our study was to verify whether local ALP activity can be held as a marker of fibrosis in chronic interstitial lung disorders. ALP was determined in the bronchoalveolar lavage of 140 subjects: 25 control subjects, and 33 patients with silicosis, 38 with idiopathic pulmonary fibrosis (IPF), and 18 with Stage I, 16 with Stage II, and 10 with Stage III/IV sarcoidosis. We observed a significant augmentation of ALP activity in patients with IPF, as well as in those with Stages II and III/IV sarcoidosis. Albumin was higher in those with Stages I and II sarcoidosis, but it was normal in the other groups. Therefore, a significant increase in ALP:albumin ratio characterized IPF (median, 10.3; range, 2.4 to 83.2) and Stage III/IV sarcoidosis, (8.9, 4.4 to 103.1) as compared with Stage I (2, 1.1 to 18) and Stage II (4.7, 0.7 to 26.6) sarcoidosis, silicosis (6.5, 0.5 to 42.7), and the nonsmoker (6.1, 2.9 to 12.9) and smoker (6.4, 2 to 15.2) control groups. We conclude that an increase of the ALP: albumin ratio in bronchoalveolar lavage fluids from patients with chronic interstitial disorders may reflect a fibrosing progression.

Adult↗
PubMed1997

Identification of human pulmonary alkaline phosphatase isoenzymes.

An increase of alkaline phosphatase (ALP) activity has been observed in the bronchoalveolar lavage fluid (BALF) of patients affected by pulmonary fibrosis in chronic interstitial lung disorders. To characterize the ALP isoenzymes in such cases, we used gel filtration, agarose gel electrophoresis, heat and amino acid inhibition assays, wheat-germ agglutinin (WGA) precipitation, and an immunoassay specific for the bone-isoform of ALP. Only one anodic band representing a high-molecular-weight isoform of ALP (Mr approximately 2,000 kDa) was observed on electrophoresis of BALF. The inhibition assay results were consistent for a tissue-nonspecific isoenzyme sensitive to a temperature of 56 degrees C (71.9 +/- 2.5% inhibition) and to homoarginine (65.7 +/- 1.9%), and resistant to L-phenylalanine and L-leucine. Less than 13% of ALP activity was heat-stable. After incubation of BALF specimens with glycosyl-phosphatidylinositol-phospholipase D plus Nonidet P-40, or with phosphatidylinositol-phospholipase C alone, an electrophoretic cathodic band (Mr approximately 220 kDa) appeared near the bone band of a standard serum. With the WGA assay, 84.4 +/- 3.3% of ALP precipitated and the band disappeared. After immunoassay for the bone isoform, a mean of less than 5% enzyme activity was measured. We conclude that the ALP found in BALF is a pulmonary isoform of a tissue nonspecific isoenzyme.

Adult↗
PubMed1997

Comparison of invasive and noninvasive saturation monitoring in prescribing oxygen during exercise in COPD patients.

The aim of this study was to determine whether it is possible using ear-oximetry to prescribe the correct oxygen flow rates during exercise in chronic obstructive pulmonary disease (COPD) patients on long-term oxygen therapy (LTOT). Twenty COPD patients on LTOT, with exercise desaturation breathing oxygen at resting flow rates, performed a series of 6-min treadmill walking tests, with a progressive increase in oxygen flows until oxygen saturation measured by ear- or pulse-oximetry (Sp,O2) was above 90%. The exercise studies were repeated the next day, saturation being measured both noninvasively by ear-oximetry (Sp,O2) and invasively by CO-oximeter (Sa,O2). The exercise studies continued until both Sa,O2 and Sp,O2 were above 90%. Reproducibility and agreement of the results were analysed according to Bland and Altman. Sp,O2 was significantly lower than Sa,O2 by, on average, 0.7% (p < 0.004). Sp,O2 reproducibility between the two days was good. The invasive and noninvasive oxygen flow prescriptions agreed in only 10 subjects; in six subjects ear-oximetry over-estimated the oxygen supply (p < 0.0005), whilst in four subjects it underestimated (p < 0.01). Contingency table analysis with coded raw data for the values of the sixth minute (that of the deepest desaturation) showed poor agreement between CO- and pulse-oximetry (Chi-squared p < 0.003). However, theoretically, if the Sp,O2 target had been raised to 93%, there would have been hardly any underestimations of Sa,O2 p = NS). We concluded that noninvasive measurement of oxygen saturation is not adequate for estimating arterial saturation in chronic obstructive pulmonary disease. We suggest, as a working solution, that a new cut-off limit of 93% oxygen saturation measured by pulse oximetry should be used as the value below which exercise-induced desaturation should be corrected in order to allow oxygen to be properly prescribed during activities of daily life.

Exercise Test↗
PubMed1997

Pulmonary failure as a cause of death in COPD.

Data on the outcome of patients with chronic obstructive pulmonary disease (COPD) are limited. We know that the prognosis is poor when respiratory insufficiency develops, but we have little information on the actual cause of death. Epidemiological studies are suitable for the assessment of the prevalence of the disease, but give no details on the actual cause of death. Age and forced expiratory volume in one second (FEV1) have been recognized as the best predictors of mortality in studies designed to quantify survival of COPD patients, particularly when the post-brochodilator value is used, as this provides a better estimate of airway and parenchymal damage. Data from Intensive Care Units on acute respiratory failure have several significant limitations. Firstly, it is probable that some patients elect not to undergo intensive treatment for a terminal bout of respiratory failure, particularly if it is not first episode. Secondly, the actual cause of death is often not described in adequate detail. Hypoxaemia and acidaemia are the main risk factors in acute exacerbation of the disease and the presence of pulmonary infiltrates on chest radiographs worsens the prognosis. A single bout of respiratory failure appears to have no effect on the prognosis of COPD patients after recovery, but there is a consistent increase in mortality after the second episode. It seems possible to manage the majority of episodes of acute respiratory failure with mechanical ventilation administered with noninvasive techniques. When endotracheal intubation is necessary, the prognosis is usually poor and the survival after 1 yr is usually lower than 40%. The role of long-term home mechanical ventilation is still unclear. Results from pivotal studies have been encouraging, although survival is far less impressive than in neuromuscular disorders. In patients with end-stage lung disease, lung transplantation can be considered the only possibility of increasing pulmonary functional capacity. However the technique is reserved only for a highly selected group of patients and data on the long-term outcome are awaited.

Acute Disease↗