Carlo Giuntini

Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism

Abstract: We followed prospectively 834 consecutive patients (70% inpatients), evaluated for suspected pulmonary embolism, for a median time of 2.1 years (range, 0-4.8 yr), and compared the survival rates in patients with proven pulmonary embolism (n = 320) with those without (n = 514). In multivariate analysis, we modeled the probability of surviving in patients with pulmonary embolism as a function of the extent of pulmonary vascular obstruction at baseline. Among patients with pulmonary embolism, a scintigraphic follow-up was pursued to assess the restoration of pulmonary perfusion over a 1-year period. We found that massive pulmonary embolism (vascular obstruction ≥50%) is a risk factor for mortality within the first few days after onset but, subsequently, has no significant effect on survival. The adjusted risk of death in patients with massive pulmonary embolism was 8-fold higher than in patients without embolism within the first day after the incident event. By contrast, the adjusted risk of death for patients with minor or moderate pulmonary embolism (vascular obstruction <50%) was no higher than in patients without embolism at any time after onset. Most of the patients who survived a year after pulmonary embolism showed a nearly complete restoration of pulmonary perfusion with a considerable improvement in arterial oxygenation. Four (1%) of the 320 patients with pulmonary embolism at presentation developed chronic thromboembolic pulmonary hypertension. These patients featured persistent large perfusion defects in sequential lung scans. Pulmonary embolism with vascular obstruction ≥50% is a strong, independent predictor of reduced short-term survival. This underscores the need for a prompt diagnosis of the disease. Monitoring the resolution of pulmonary embolism by lung scanning may prove useful in identifying patients with persistent perfusion abnormalities who may be at risk of chronic thromboembolic pulmonary hypertension.

Lung involvement in essential mixed cryoglobulinemia

Abstract Lung function studies were performed in 23 patients with the syndrome of essential mixed cryoglobulinemia. Signs of exposure to hepatitis B virus were present in nine (HBV+) and absent in 14 (HBV−). Pulmonary symptoms were generally absent or moderate except in three patients who presented with either asthma, hemoptysis or pleurisy together with the other manifestations of the disease. On the contrary, tests indicative of small airways disease, such as forced end-expiratory flow (FEF 0.75-0.85VC ) and maximal expiratory flow at low lung volume (Vmax 0.75VC ) were markedly altered (61.9 per cent and 40.4 per cent of the expected values, respectively). Other lung function tests, such as residual volume (RV), airway resistance (Raw), FEF 0.25-0.75VC , maximal expiratory flow at 50 per cent vital capacity (VC)(Vmax 0.50VC ) showed smaller deviations from normal, whereas vital capacity (VC), total lung capacity (TLC), forced expiratory volume in 1 second (FEV 1 ), FEV 1 :VC, RV:TLC and intrathoracic gas volume (ITGV) were within the normal limits. Nine of 14 of the HBV− patients showed impairment of gas exchange, measured as alveoloarterial oxygen gradient D(A-a)O 2 , which, on the contrary, was always within normal limits in the nine HBV+ patients. The difference between the two groups was significant (28.4 mm Hg and 18.6 mm Hg, respectively, p

Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.

Fibrinolytic Effects of Urokinase and Heparin in Acute Pulmonary Embolism: A Randomized Clinical Trial

Dissolution of pulmonary emboli with heparin and urokinase is ascribed, respectively, to anticoagulation and fibrinolysis. Since truly independent assessment of these effects in man is lacking, we administered each drug alone. Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three randomized groups of 10 patients each: groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase, respectively, and group B who received heparin. After 6 h of treatment, fibrinogen fell in all the groups, while, after 12 h, remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly. Up to 60 h, statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion. These observations suggest that heparin may induce a lytic state. As to signs of pulmonary emboli resolution, no differences between groups were found in lung perfusion and gas exchange recovery at any time (from 1 day to 1 year) and in pulmonary artery pressure reduction at 1 week. The greater angiographic and scintigraphic recovery observed with urokinase, versus heparin alone, after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out. The indications of heparin and urokinase should be evaluated in the light of these results.

Prognosis of occupational asthma

Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed. Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but non-specific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis.

Skin prick test reactivity to common aeroallergens in relation to total IgE, respiratory symptoms, and smoking in a general population sample of northern Italy.

Skin prick test (SPT) reactivity to common airborne allergens and its relationships to sex, age, smoking habits, and respiratory symptoms/ diseases were evaluated in a general population sample (n= 2841, 8–75 years of age) living in the Po delta area (northern Italy). Subjects completed a standardized questionnaire and underwent prick tests (12 local allergens, a negative and a positive control) and determination of total serum IgE. Atopy was evaluated by measuring the maximal diameter for each allergen, after subtracting that of the negative control. Thirty‐one percent of subjects showed a positive skin response at a 3‐mm threshold. Pollens, Dermatophagoides pteronyssinus, and D. farinae caused the highest frequencies of reactions. Young people and those who had never smoked had higher prevalence rates of SPT reactivity. Asthma, asthma symptoms, and rhinitis were significantly associated with SPT reactivity in both sexes (cough only in females) and with the number of positive reactions. IgE values were also significantly associated with SPT reactivity. In conclusion, our findings indicate that almost one‐third of the general population of an Italian rural area is skin test positive, emphasizing the importance of assessing atopy in respiratory epidemiologic surveys.

Identification of a predominant COPD phenotype in clinical practice

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by small airways increased resistance and/or terminal airspaces emphysematous destruction. Spirometric detection of not fully reversible airflow limitation unifies under the acronym COPD, a spectrum of heterogeneous conditions, whose clinical presentations may be substantially different. In a cross-sectional study we aimed to ascertain whether COPD phenotypes reflecting different mechanisms of airflow limitation could be clinically identified. METHODS Multidimensional scaling was used to visualize as a single point in a two-dimension space the multidimensional variables derived from each of 322 COPD patients (derivation set) by clinical, functional, and chest radiographic evaluation. Cluster analysis assigned then a cluster membership to each patient data point. Finally, using cluster membership as dependent variable and all data acquired as independent variables, we developed multivariate models to prospectively classify another group of 93 COPD patients (validation set) in whom high-resolution computerized tomography (HRCT) density parameters were measured. RESULTS A multivariate model based on nine variables acquired from the derivation set by history (sputum characteristics), physical examination (adventitious sounds, hyperresonance), FEV1/VC, and chest radiography (increased vascular markings, bronchial wall thickening, increased lung volume, reduced lung density) partitioned the validation set into two groups whose clinical, functional, chest radiographic, and HRCT characteristics corresponded to either an airways obstructive or a parenchymal destructive COPD phenotype. CONCLUSION Patients with COPD can be assigned a clinical phenotype reflecting the prevalent mechanism of airflow limitation. The standardized identification of the predominant phenotype may permit to clinically characterize COPD beyond its unifying spirometric definition.

Comparison between hypertonic and isotonic saline-induced sputum in the evaluation of airway inflammation in subjects with moderate asthma

Background Hypertonic saline‐indueed sputum has recently been used for the evaluation of airway inflammation in asthma.

Venous Obstruction in Permanent Pacemaker Patients: An Isotopic Study

Isotope venography was used to study the venous circulation proximal to the superior vena cava in two groups of pacemaker patients, one with a single endo‐cavitary electrode and the other with multiple pacing catheters. A control group of patients without pacemakers was also studied. Numerous abnormalities were found, especially in the group with multiple electrodes. These findings suggest that venous obstruction is a common complication of endocardial pacing.

The Po River Delta epidemiological study of obstructive lung disease: sampling methods, environmental and population characteristics.

A longitudinal study on chronic obstructive lung disease (AOD) has been started in the Po River Delta in northern Italy. The first cross-sectional study was conducted in this previously unpolluted rural area before the start of operation of a large thermoelectric power plant (2,649 megawatt). A significant output of air pollutants is expected. This will permit us to carry out a “natural experiment” to study the effects of air pollutants (SO2 and suspended particulates). A multistage stratified cluster design was chosen. Stratification was based on age and socio-economic characteristics (SES) of households, and was performed in two steps, using the different indices computed from the census data. Geographic zones represented four areas of different predicted pollution exposure, once the plant started operating. There were 3,289 subjects in the selected age group (8–64) who agreed to participate (78%); only 11% refused to participate. The participants were representative of the clusters and SES. Participants had slightly fewer employed males, who did not participate due to work. The stratification and staging method allowed us to keep an acceptable level of precision and efficiency in the sample. In fact age-related differences were not found among the SES strata and geographic zones; various socio-economic characteristics, verified from the questionnaire information, were consistent with the SES stratification. Differences between geographic zones were related to the number of households of different SES within clusters; however this reflects the characteristics of the general population in the area.