Maurizio Dottorini

Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma

BACKGROUND Nocturnal awakening is a common feature of bronchial asthma, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether nocturnal awakening is associated with changes in platelet function with the use of a variety of markers of platelet activation. METHODS Ten patients with a history of nocturnal asthma and 10 age- and sex-matched healthy control subjects were studied at 10:00 PM, 4:00 AM, and 10:00 AM on 2 consecutive days. The following parameters were tested: forced expiratory volume in 1 second (FEV1), log dose of methacholine inducing a 20% fall in FEV1, platelet count and volume, platelet aggregation induced by collagen or activating factor, and plasma and intraplatelet levels of beta-thromboglobulin and platelet factor 4. RESULTS We have demonstrated that altered platelet function and platelet activation occurs at 4:00 AM in patients with nocturnal asthma and is associated with the maximum increases in bronchial reactivity. Such changes were not observed in 10 control subjects. Platelet dysfunction has been detected as a reduced aggregatory response of platelets to collagen and platelet activating factor such that up to 5 times more platelet activating factor and 1.5 times more collagen were required to elicit a threshold aggregatory response in asthmatic subjects when compared with control subjects; this difference was evident at all time points tested. Furthermore, at 4:00 AM there were significantly lower levels of intraplatelet beta-thromboglobulin corresponding to the maximum reduction in peak expiratory flow and to the maximal increase in bronchial responses to inhaled methacholine. CONCLUSIONS These results suggest that platelet activation accompanies nocturnal asthma and further suggest that platelets may play a role in this common clinical condition.

Laryngeal cancer: long-term follow-up of respiratory functions after laryngectomy

Pulmonary function of 31 heavy smokers with laryngeal cancer was evaluated before and during the 1st year after total (n = 21) and conservative (n = 10) laryngectomy. 2 of them died because of recurrences, 1 for bronchopulmonary complications. Long-lasting hoarseness was the only presenting symptom in all patients. Preoperative lung function data and mucociliary clearance were consistent with a coexisting chronic obstructive lung disease in most subjects and was probably due to smoking. No differences were observed comparing pre- and postoperative data in the 10 conservative laryngectomy patients. On the contrary, the total-laryngectomy patients showed a progressive impairment of bronchial obstruction and bacteriological infection of the trachea during the 1st year after the operation. An impressive increase in mucociliary clearance rates has been observed 2 months after total laryngectomy during the postoperative hypersecretory phase. the obtained data allow us to hypothesize that when clinical conditions of laryngectomized patients in whom local or distant recurrences have been excluded deteriorate, this is related to a progressive bronchial obstruction at any level of the bronchial tree due to descending bacterial infection of the airways. To our knowledge this is the only work demonstrating that total laryngectomized patients need a complete pre- and postoperative evaluation of lung function, airway dynamics, mucociliary function and tracheal bacteriology for long-term prognosis and treatment.

Mild prematurity and respiratory functions

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years; mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P<0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.

Pulmonary function studies in adenoid hypertrophy

Tests of pulmonary function were performed on children with severe adenoid hypertrophy, before and one month after adenoidectomy. Five types of subjects were selected: (1) normal; (2) cases with isolated increase of residual volume (RV); (3) supernormal type with increased RV; (4) obstructive type of ventilatory defect, and (5) restrictive type of ventilatory defect. Following adenoidectomy there is an objective evidence of improved pulmonary function. The data suggest that 65.7% of clinically normal children with adenoid hypertrophy show pulmonary function abnormalities.

Circadian Rhythms of Respiratory Functions in Asthmatics

35 subjects underwent pulmonary function tests, plasma cortisol and urinary catecholamine measurements at 4-hour intervals, during a period of 24 h. In healthy subjects a circadian variation was not demonstrated. In asthmatic subjects circadian variation of a large number of ventilatory variables and a normal circadian pattern for plasma cortisol were demonstrated. Asthmatic patients were divided into two groups: patients with intrinsic asthma and patients with extrinsic asthma. The former showed the most impressive circadian pattern; the most severe bronchospasm occurred between 12.00 and 00.00 h; patients with extrinsic asthma, older than 20 years became worse around 03.00 h. During this period their urinary catecholamines reached the lowest values. The younger patients with extrinsic asthma presented the highest TGV values at 12.50 h. From the clinical viewpoint, it is emphasized that chronobiologic criteria could be utilized for the chronotherapeutic management of asthmatics.

Normal Reference Values for Regional Pulmonary Peripheral Airspace Epithelial Permeability

Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smokers lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.

Reference Values for Flow-Volume Curves during Forced Vital Capacity Breathing in Male Children and Young Adults

127 non-smoking males aged 8-25 years were studied to obtain normal reference values for flow-volume (FV) curves. Analysis of variance (ANOVA) showed significant differences for all indices (PEF; MEF 25%, 50%, 75%; PIF; MIF 25%, 50%, 75%) in the first three age-groups (8-10, 11-13 and 14-16 years); the three last groups (17-19, 20-22 and 23-25 years) did not show any significant variation of FV curve data. Male subjects older than 16 years showed a negative correlation between maximal expiratory flow at 50% of forced vital capacity and standing height. Multiple regression equations relating FV curve indices to age and anthropometric data are calculated.

Myasthenic Inspiratory Vocal Cord Dysfunction: Efficacy of Nasal Continuous Positive Airway Pressure Treatment

Myasthenic vocal cord dysfunction (VCD), presenting with severe inspiratory stridor, was successfully treated with nasal continuous positive airway pressure (nCPAP), thus giving the medical staff time to make the diagnosis and avoiding intubation or tracheostomy. An important sign leading to diagnosis was the very high MEF50/MIF50 ratio calculated from the flow-volume loop. nCPAP treatment induced prompt remission of stridor and a sharp reduction in the MEF50/MIF50 ratio from 9.90 to 1.36. A review of the literature has shown that VCD with inspiratory stridor is an unusual onset symptom of myasthenia gravis and that nCPAP treatment may avoid emergency oral/tracheal intubation and tracheostomy. After diagnosis, the patient underwent thymectomy, and today, 3 years later, he is well without any further therapy.

Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree

Human albumin microspheres (99mTc-HAM; 7–25µm) and spherocytes (99mTc-S; 4–4.5µ) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physicalchemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.

Biodegradability of inhaled organic particles in patients with chronic bronchitis

2 h after the inhalation of monodispersed 99mTc-labeled autologous spherocytes and of commercial human albumin microspheres (HAM), 7 patients with chronic bronchitis underwent bronchofibroscopy. The fate of organic particles along the tracheobronchial tree was verified by scanning electron microscopy and the proteolytic activity (trypsin and PZ peptidase) in mucus samples was assessed. Significant proteolytic activity was detected in bronchial secretions. Thereafter in vitro digestion of labeled spherocytes and HAM was verified after exposure to increasing concentrations of trypsin. While in vitro a similar time-course of tryptic digestion of both particles was observed, in vivo spherocytes seem to be less vulnerable to enzymatic digestion. These findings add another unexpected variable, which may influence the reproducibility of radioaerosol lung mucociliary clearance measurements, and improve its standardization.