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M Saetta

Publications and source records attributed to M Saetta.

At least 19 recordsLinked to original sources
PubMed1992

Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma.

We have studied the phenotype and activation status of leukocytes in the bronchial mucosa in patients with isocyanate-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with occupational (five toluene- and four methylene diisocyanate-sensitive) asthma, 10 subjects with extrinsic asthma, and 12 nonatopic healthy control subjects. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase method. There was a significant increase in the number of CD25+ cells (interleukin-2 receptor-bearing cells, presumed "activated" T-lymphocytes; p less than 0.01) in isocyanate-induced asthma compared with that of control subjects. There were also significant increases in major basic protein (BMK-13)-positive (p less than 0.02) and EG2-positive (p less than 0.01) cells that represent total and "activated" eosinophil cationic protein-secreting eosinophils, respectively. In agreement with our previous findings, CD25+ (p less than 0.01), BMK-13 (p less than 0.03), and EG2+ (p less than 0.01) cells were also elevated in extrinsic asthma. No significant differences were observed in the numbers of T-lymphocyte phenotypic markers (CD3, CD4, and CD8) between subjects with asthma (isocyanate-induced and extrinsic) and control subjects. Similarly, no significant differences in immunostaining for neutrophil elastase (neutrophils) or CD68 (macrophages) were observed. The results suggest that isocyanate-induced occupational asthma and atopic (extrinsic) asthma have a similar pattern of inflammatory cell infiltrate. The results support the view that T-lymphocyte activation and eosinophil recruitment may be important in asthma of diverse etiology.

Adult↗
PubMed1992

Airway mucosal inflammation in occupational asthma induced by toluene diisocyanate.

We examined the light and electron microscopic structure of lobar bronchial biopsies of nine subjects with occupational asthma induced by toluene diisocyanate (TDI) and of four control nonasthmatic subjects who had never been exposed to TDI. Inflammatory cell numbers were separately assessed in the intact epithelium, in the more superficial layer of the submucosa, and in the total submucosa. Asthmatic subjects had an increased number of inflammatory cells in the airway mucosa compared with control subjects. Eosinophils were significantly increased in all compartments, CD45-positive cells were significantly increased in the epithelium and in the more superficial layer of the submucosa, and mast cells were significantly increased only in epithelium. By electron microscopy eosinophils and mast cells appeared degranulated only in asthmatic patients. In the areas of epithelium that appeared intact by light microscopy, electron microscopy showed that, although the intercellular spaces between columnar cells were similar in asthmatic and control groups, the intercellular spaces between basal cells were significantly wider in patients with asthma. Patients with TDI-induced asthma also had a thicker subepithelial reticular layer, where immunohistochemistry showed the presence of collagen III. In conclusion, in patients with asthma induced by TDI, the airway mucosa shows pathologic features, such as inflammatory cell infiltrate and thickening of subepithelial collagen, similar to those described in atopic asthma.

Adolescent↗
PubMed1992

Effect of cessation of exposure to toluene diisocyanate (TDI) on bronchial mucosa of subjects with TDI-induced asthma.

The effect of cessation of exposure to toluene diisocyanate (TDI) was studied in six patients with TDI-induced asthma, proved by a positive inhalation challenge with TDI. Bronchial challenges with TDI and methacholine were performed, and lobar bronchial biopsies were taken at diagnosis and 6 months later, after cessation of exposure. Biopsies from four nonasthmatic control subjects were also examined. At diagnosis, asthmatic subjects had thickened reticular basement membrane (p less than 0.05) and increased numbers of mononuclear cells (p less than 0.05) and eosinophils (p less than 0.05) in the lamina propria when compared with control subjects. Electron microscopy showed degranulation of eosinophils and mast cells in asthmatics. Six months after cessation of exposure, the thickness of reticular basement membrane was significantly reduced compared with that at diagnosis (p less than 0.05), and it decreased to values similar to those of control biopsies. Inflammatory cell numbers in bronchial mucosa of asthmatic subjects did not change significantly 6 months after removal from exposure, and degranulation of eosinophils and mast cells was still present. At the end of the study, airway hyperresponsiveness to methacholine and/or sensitivity to TDI persisted in most of the asthmatic patients despite the cessation of exposure and the disappearance of asthmatic symptoms. In conclusion, in patients with occupational asthma induced by TDI, the avoidance of exposure to the sensitizing agent for 6 months is able to reverse the reticular basement membrane thickening in the bronchial mucosa, but the inflammatory cell infiltrate, the specific sensitivity to TDI, and the nonspecific airway hyperreactivity may persist.

Adult↗
PubMed1992

The effect of phosphoramidon and epithelium removal on toluene diisocyanate-induced contractions in guinea-pig bronchi.

To evaluate the role of airway neutral endopeptidase 24.11 (NEP) and epithelium removal in the contraction of airway smooth muscle in response to toluene diisocyanate (TDI), we studied the effects of the NEP inhibitor, phosphoramidon, on TDI-induced contractions of guinea-pig bronchial rings with intact epithelium and without epithelium. In preparations with intact epithelium, phosphoramidon (10 microM) potentiated the contractile response to TDI (0.3 mM) (mean +/- SEM, 23.7 +/- 2.5% versus 67.9 +/- 10.3%, p less than 0.01). Phosphoramidon also increased TDI-induced contractions in tissues without epithelium (36.9 +/- 4.9% versus 52.5 +/- 7.1%, p less than 0.05). Removal of the epithelium increased the contractile response to TDI (23.7 +/- 2.5% versus 36.9 +/- 4.9%, p less than 0.05). These results demonstrate the response to TDI is increased in epithelium-free compared to intact bronchi and that NEP 24.11 modulates the effects of endogenously released tachykinins by TDI at all of the sites where NEP is found in the airways.

Animals↗
PubMed1991

Late asthmatic reactions, airway inflammation and chronic asthma in toluene-diisocyanate-sensitized subjects.

To determine the importance of airway inflammation for exacerbation and prognosis of asthma induced by toluene diisocyanate (TDI), we first examined sensitized subjects during asthmatic reactions induced by exposure to TDI in the laboratory. We observed that late and dual, but not early, asthmatic reactions induced by TDI are accompanied by a transient increase of airway responsiveness, bronchoalveolar neutrophilia followed by eosinophilia and by an increase of LTB4 and albumin in bronchoalveolar lavage fluid. All these effects were prevented by pretreatment with prednisone. In addition, we examined the lung pathology of 1 sensitized subject who died after exposure at work. The pathologic features of fatal asthma induced by TDI and of chronic asthma induced by TDI suggest the importance of inflammation for the exacerbation and prognosis of the disease.

Asthma↗
PubMed1991

Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma.

The peripheral airways and the adjacent muscular pulmonary arteries were studied by morphometric methods in the autopsy lungs of six asthmatic subjects who died suddenly during an asthma attack, and they were compared with those of six control subjects who died of other causes and had no history of respiratory diseases. Bronchioles of asthmatic subjects had an increased amount of lumen occlusion (p less than 0.01), smooth muscle thickness (p less than 0.001), and inflammatory infiltrate (p less than 0.001), and both mononuclear cells and eosinophils contributed to this increased inflammation. The muscular pulmonary arteries adjacent to occluded and inflamed bronchioles did not have the morphologic features of chronic hypoxia, as shown by the normal medial and intimal thickness, but they had an important inflammatory process in their walls that was particularly marked at sites adjacent to airways. Although the functional significance of these findings is unknown, they may be responsible in part for the gas exchange abnormalities observed in acute severe asthma.

Adolescent↗
PubMed1991

Airway inflammation during late asthmatic reactions induced by toluene diisocyanate.

To determine the importance of airway inflammation for the development of late asthmatic reactions, we examined sensitized subjects during late asthmatic reactions induced by exposure to toluene diisocyanate (TDI) in the laboratory. Late asthmatic reactions are associated with a transient increase of bronchial responsiveness and, at the same time, with an increase of neutrophils followed by eosinophils, and of LTB4 and albumin in bronchoalveolar lavage fluid. Late asthmatic reactions, increased bronchial responsiveness, and increase of neutrophils, eosinophils, LTB4, and albumin concentration in bronchoalveolar lavage induced by exposure to TDI are all prevented by pretreatment with prednisone but not with the nonsteroidal anti-inflammatory agent indomethacin. Aerosolized steroids (beclomethasone and dexamethasone isonicotinate) completely inhibit late asthmatic reactions induced by TDI, whereas theophylline has a partial, and verapamil, ketotifen, and cromolyn have no protective effect. These results suggest that late asthmatic reactions induced by TDI may be caused by airway inflammation, and that anti-inflammatory steroids should be recommended in the prophylaxis of TDI asthma.

Asthma↗
PubMed1989

Assessment of induced bronchoconstriction in anesthetized cats by the end-inflation occlusion method.

Airway occlusion during constant flow inflation allows rapid determination of frequency-dependence of pulmonary resistance by estimating its extreme values: RL,max (zero frequency) and RL,min (high frequency). RL,max represents the maximum resistance value that can be obtained with the prevailing time constant inequalities and stress relaxation, while RL,min represents the resistance that would be obtained in the absence of time constant inequalities and stress relaxation. In 5 anesthetized, tracheostomized, paralyzed, and artificially ventilated cats, RL,min, RL,max, and static pulmonary elastance (EL,st) have been measured following airway occlusion at the end of constant flow tidal inflations. Measurements were made before and during continuous infusion of increasing doses of serotonin (10-100 micrograms/kg/min IV). The development of intrinsic positive end-expiratory pressure (PEEPi) was also assessed. Cats varied greatly in their responsiveness to serotonin, but RL,min, RL,max, and EL,st increased and PEEPi developed in all cats. Increases in RL,max did not always parallel increases in RL,min but were similar to those in EL,st, suggesting that altered viscoelastic properties of the lung contributed to the increases in RL,max. We conclude that time-constant inequalities, changes in the lung periphery, and hyperinflation probably all contribute to the observed increases in RL,max and will influence conventional methods of measuring RL. Measuring RL,min potentially provides a better method for assessing the reduction in caliber of the conducting airways in isolation.

Airway Obstruction↗
PubMed1989

Response to acetylcholine and myosin content of isolated canine airways.

Contractility of tracheal smooth muscle strips and spiral strips of fourth to fifth generation bronchi was studied in organ baths. The relationship among contractility, airway smooth muscle myosin, and smooth muscle thickness was also examined. The trachea was divided into three segments, each consisting of 12-14 rings. Smooth muscle strips from each of the three regions (top, middle, and bottom of the trachea) and from fourth to fifth generation bronchi were studied. Acetylcholine (ACh) sensitivity (-log EC50) was 8.1, 7.1, 7.9, and 6.1 for the top, middle, and bottom of the trachea and the bronchi, respectively. At P = 0.01, the EC50 ACh value of the top of the trachea differed from the EC50 value of the bronchi. Maximal tension (Tmax) generated in bronchi (3.2 g) was lower (P less than 0.01) than in the top (10.4 g), middle (7.1 g), and bottom of the trachea (5.1 g). Differences between trachea and bronchi disappeared when Tmax was corrected for smooth muscle myosin content. Thickness of smooth muscle in bronchi was less (P less than 0.01) than in the three regions of trachea. Tmax was significantly correlated with airway smooth muscle thickness (r = 0.56; P less than 0.05). These results suggest that in mongrel dogs sensitivity to ACh shows a gradient from the top of the trachea to the bronchi and that Tmax is greater in the trachea than in the bronchi and is significantly correlated with thickness of smooth muscle.

Acetylcholine↗
PubMed1989

Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records.

We report the sudden death of a 16 yr old boy with asthma. At presentation, the patient had symptoms of active asthma, mild bronchoconstriction, severe airway hyperresponsiveness to methacholine, and increased variability of peak expiratory flow records. After the patient was placed on inhaled beclomethasone (1 mg b.i.d preceded by inhaled fenoterol 0.4 mg b.i.d) he rapidly felt better, lung function improved, but airway responsiveness remained severe. Four months later, on the day he died, he was well until a fatal attack of asthma occurred around midnight without identifiable precipitating factors. Taken to hospital, he was dead on arrival. Necroscopy and microscopy showed the characteristic features of asthma death. This case report suggests that; a) asthma death may occur suddenly and unexpectedly; b) asthma death may not be prevented by long-term treatment with high-dose inhaled beclomethasone; c) severe bronchial hyperresponsiveness, even in the presence of stable peak flow records, may identify asthmatic patients at risk of sudden death.

Adolescent↗
PubMed1989

Pathology of bronchial asthma and animal models of asthma.

We reviewed studies on pathology of status asthmaticus, asymptomatic asthma, and of animal models developed to study the pathogenesis of asthma. In status asthmaticus airway occlusion by mucous plugs, desquamed epithelium, goblet cell hyperplasia, submucosal glands hypertrophy, increased smooth muscle, basal membrane thickening, inflammatory infiltration of the bronchial mucosa are observed, together with focal areas of alveolar wall destruction in lung parenchyma. At variance with active asthma, in which almost invariably inflammatory cells infiltrate the mucosa, only scarce airway inflammation is reported in asthmatics between attacks. The majority of the animal models developed so far have been addressed to investigate the mechanism of the transient hyperreactivity that is associated with exacerbations of asthma, while little information is available on the structure-function relationship on long-lasting hyperresponsiveness.

Airway Obstruction↗
PubMed1989

Fatal asthma.

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Asthma↗
PubMed1988

Fatal asthma in a subject sensitized to toluene diisocyanate.

We report the case of a 43-yr-old car painter who died within 1 h of exposure to a polyurethane paint in the workplace. A diagnosis of asthma induced by toluene diisocyanate (TDI) had been established 6 yr before, when he underwent inhalation challenges with carbachol and with TDI. The subject had airway hyperresponsiveness to carbachol (PD20FEV1 carbachol = 0.32 mg; normal value greater than 1.0 mg) and developed an early and long-lasting asthmatic reaction after exposure to TDI in the laboratory. Although it was recommended that he change his job or stop using paints containing isocyanates, he continued to work as a car painter, taking antiasthmatic drugs both at work and at home to control asthma symptoms. On Monday, October 6, 1986, at 11:30 A. M., he developed a severe attack of asthma while he was mixing the 2 components of a polyurethane paint. Taken to hospital, he was dead on arrival. Autopsy showed no evidence of cardiac or brain disease; lungs were overinflated, the cut surface showed grey glistening mucous plugs in in the airways. Histologic examination showed denudation of airway epithelium and thickening of the basement membrane with infiltration of the lamina propria by polymorphonuclear leukocytes, mainly eosinophils, and diffuse mucous plugging of bronchioles. Bronchial smooth muscle appeared hyperplastic and disarrayed, and lung parenchyma showed focal areas of alveolar destruction adjacent to areas of perfectly intact alveolar walls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Cold exposure of the pregnant rat and neonatal respiration.

Pregnant rats were exposed to a cold environment (4 degrees C for almost the whole pregnancy) and the effects on the newborn rats' ventilation, metabolic rate and morphological lung appearance were examined. In cold-exposed rats oxygen consumption (VO2) increased during pregnancy and was 23% more than in control rats 1 day after delivery. All pups were born at term in litters of similar size. At 2-4 days after birth, in the pups born from cold-exposed mothers ("cold" pups), body weight (BW) and lung weight (LW) were reduced, with respect to control newborns, in a similar proportion. In "cold" pups the mean chord of subpleural alveoli was larger and lung volume smaller than in control pups. Both specific minute ventilation (VE/kg), measured by flow plethysmography, and specific oxygen consumption (VO2/kg), measured manometrically, were similar between the two groups. However, tidal volume/BW was smaller and breathing frequency higher in "cold" pups, a breathing pattern which appears necessary to fulfil normal metabolic requirements despite lung immaturity. These results suggest that cold exposure during pregnancy represents a maternal stress which results in somatic and pulmonary underdevelopment of the neonate.

Animals↗
PubMed1987

Postnatal development of the lung following denervation.

We asked to what extent pulmonary innervation influences the postnatal development of the lung. To this end we performed cervical vagotomy and sympathectomy either on the right or on the left side in young rats and rabbits and rats after weaning. One to four weeks later we examined the lungs of the denervated side, the contralateral intact side of the same animal, and sham-operated controls. Dry lung weight, lung volume and the size of subpleural alveoli were not different among the three groups. Lung mechanical properties (static and dynamic lung compliances, lung resistance, frequency dependence of compliance), measured in rabbits, were also not different among groups of lungs, suggesting that neither central nor peripheral airways were markedly affected by the denervation. The breathing pattern, measured in the rats after weaning, was characterized by a larger tidal volume in the denervated animals than in controls, as expected after the partial pulmonary afferent denervation. The absence of major structural and functional changes in the lungs of these animals suggests that an increase in the mechanical stretch to the lung above that normally occurring during resting breathing does not influence the lung structure. We conclude that pulmonary innervation does not play an important role in the postnatal development of the lung.

Animals↗
PubMed1987

Interaction of hypoxic and hypercapnic stimuli on breathing pattern in the newborn rat.

We aimed to investigate whether newborn rats respond to acute hypoxia with a biphasic pattern as other newborn species, the characteristics of their ventilatory response to hypercapnia, and the ventilatory response to combined hypoxic and hypercapnic stimuli. First, we established that newborn unanesthetized rats (2-4 days old) exposed to 10% O2 respond as other species. Their ventilation (VE), measured by flow plethysmography, immediately increased by 30%, then dropped and remained around normoxic values within 5 min. The drop was due to a decrease in tidal volume, while frequency remained elevated. Hence, alveolar ventilation was about 10% below normoxic value. At the same time O2 consumption, measured manometrically, dropped (-23%), possibly indicating a mechanism to protect vital organs. Ten percent CO2 in O2 breathing determined a substantial increase in VE (+47%), indicating that the respiratory pump is capable of a marked sustained hyperventilation. When CO2 was added to the hypoxic mixture, VE increased by about 85%, significantly more than without the concurrent hypoxic stimulus. Thus, even during the drop in VE of the biphasic response to hypoxia, the respiratory control system can respond with excitation to a further increase in chemical drive. Analysis of the breathing patterns suggests that in the newborn rat in hypoxia the inspiratory drive is decreased but the inspiratory on-switch mechanism is stimulated, hypercapnia increases ventilation mainly through an increase in respiratory drive, and moderate asphyxia induces the most powerful ventilatory response by combining the stimulatory action of hypercapnia and hypoxia.

Animals↗
PubMed1986

Alveolar fenestrae in smokers. Relationship with light microscopic and functional abnormalities.

We studied 12 smokers' lungs with scanning electron microscopy in order to analyze the distribution and size of alveolar fenestrae and their relationship to the average distance between alveolar walls (Lm) and lung function. Alveolar fenestrae in areas near terminal airways (respiratory bronchioles and alveolar ducts) were consistently larger than fenestrae far from airways (alveoli). Fenestrae in near areas increased in size as Lm increased (r = 0.845, p less than 0.001), whereas no correlation between Lm and fenestrae size in far areas was found (r = 0.281, NS). The overall area of fenestrae (near and far) correlated significantly with FEV1 (r = -0.745, p less than 0.01), MMEF (r = -0.752, p less than 0.01), and PL90 (r = -0.804, p less than 0.05). However, when subdivided into near and far, only fenestrae near the small airways showed a significant correlation with function. These findings suggest that in smokers with mild to moderate emphysema, destruction affects preferentially the areas around the terminal airways (near areas), and these changes, although small, might play an important role in the lung function.

Aged↗