[Changes in the small airways as a long-term sequela of acute bronchiolitis and a pre-stage of chronic obstructive airway disease in adults].
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Abstract:
Apart from cigarette smoking and air pollution, lower respiratory tract infections of viral origin in early childhood are considered to be one of the risk factors for chronic obstructive lung disease. Acute bronchiolitis accounts for the typical disease of the small airways in the first two years of life. 16 symptom-free former patients have been studied 16 to 22 years after an acute attack of bronchiolitis. A complete lung function test was performed with special regard to the small airways. The volume of Isoflow proved to be the most sensitive test. The changes found are considered to be mild. Follow-up will show whether they correlate with an as yet symptom-free stage of a chronic obstructive lung disease.Keywords:
Sequela
Obstructive lung disease
Respiratory tract
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An experimental model was designed to characterize lesions in the lung of lambs inoculated with bovine respiratory syncytial virus (BRSV). 25 Merino lambs of both sexes, with a live weight of 17 +/- 3 Kg, received an intratracheal inoculation of 20 ml saline solution containing 1.26 x 10(6) TCID50 BRSV (strain NMK-7) per ml. Lambs were slaughtered 1, 3, 7, 11 and 15 postinoculation days (PID), and histopathological, immunohistochemical and electron microscopic studies were performed. Results reflected a series of lesions, the most noteworthy of which were bronchiolitis obliterants with destruction of the mucociliary apparatus, the presence of syncytial cells in alveoli and a progressive interstitial reaction. BRSV antigen was detected in lung samples. These changes might be expected to decrease the efficiency of respiratory tract defence mechanisms, rendering the lung parenchyma susceptible to opportunist bacterial infection.
Respiratory tract
Parenchyma
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We performed 211 lung function measurements on 93 children in the first year after they had been admitted with acute bronchiolitis. During the convalescent phase of the illness, 77% of the infants were hyperinflated with a thoracic gas volume greater than 40 ml/kg and 3 months later 43% were hyperinflated. Twelve months after the initial illness, 17% still had lung function abnormalities and most of these children have had lower respiratory tract symptoms. For the group as a whole about 60% have had at least one episode of wheezing. Specific conductances were significantly lower in children from atopic families, indicating worse lung function, but the significance of this finding is unclear.
Acute Bronchiolitis
Respiratory tract
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Apart from cigarette smoking and air pollution, lower respiratory tract infections of viral origin in early childhood are considered to be one of the risk factors for chronic obstructive lung disease. Acute bronchiolitis accounts for the typical disease of the small airways in the first two years of life. 16 symptom-free former patients have been studied 16 to 22 years after an acute attack of bronchiolitis. A complete lung function test was performed with special regard to the small airways. The volume of Isoflow proved to be the most sensitive test. The changes found are considered to be mild. Follow-up will show whether they correlate with an as yet symptom-free stage of a chronic obstructive lung disease.
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Obstructive lung disease
Respiratory tract
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Background Airway is one of the main routes for allergen exposure and entering airborne allergens through the airway can initiate allergic responses, resulting in development of allergic asthma. There are various environmental factors that also influence to the airway-mediated immune responses. Among the factors, respiratory syncytial virus (RSV) enables the condition of the airway to change because RSV infection is common in early life and induce the bronchiolitis. In addition, several studies have been reported that non-immune cells such as airway epithelial cells play a pivotal role in the initiation of allergic responses. The aim of our study is to determine the association between the sensitization of common airborne allergens and RSV infection in airway epithelial cells.
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The long-term prognosis following lung transplantation (LTX) depends mainly on the development of chronic rejection which appears clinically as deterioration of the lung function while, histologically, obliterative bronchiolitis (OB) is found. However, it still remains questionable whether heart-lung (HL), double or single lung (DL/SL) transplants behave similarly with regard to incidence and time pattern. Eighty-two patients, transplanted until August 92, were analyzed. Early and late deaths within 180 days postoperatively were excluded. A total of 64 patients at risk could be evaluated. By repeated lung function tests, obstructive airway disease was defined by a drop of 25% or more of the forced expiratory volume in one second (FEV1) in percent of the inspiratory vital capacity.The functional optimum after transplantation was reached after a comparable time-span postoperatively in all groups. Chronic deterioration of the lung function developed earlier following DLTX compared to HLTX and SLTX. Obstructive airway disease was diagnosed in 9/20 (45%) HL, 7/19 (37%) DL, and 7/25 (28%) SL patients. Of these, 4 died and 4 had to be retransplanted for the disease while an additional 15 patients are currently under investigation. It is concluded that the development of obstructive airway disease represents a serious problem in all types of lung transplantation. There is a tendency to earlier development following DLTX--perhaps caused by the greatest immunological potential in this group of patients.
Obstructive lung disease
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To develop a profile for the activity of lipopolysaccharides on guinea-pig lung tissue, previous in-vitro studies have been expanded to include a new model where the necessity to expose live animals is eliminated.
Isolated lung halves were perfused and tracheal spirals were immersed in Krebs solution containing lipopolysaccharides. One hour after exposure both the tracheal and pulmonary tissues were hyper-responsive to all the constrictor agents employed. This was demonstrated by the dose-response curves being shifted significantly to the left parallel to control curves. The shifts seen were comparable with those observed for bronchoconstriction after in-vivo exposure.
The results confirm that the change in airway reactivity seen after exposure to lipopolysaccharide is nonspecific and is likely to be a result of a change in reactivity of the airway smooth muscle caused either directly or indirectly by, for example, agents released from alveolar macrophages, airway epithelium or pulmonary endothelium. Changes in airway reactivity are not entirely a result of narrowing of the airway, but can arise as a result of accumulation of fluid in the airways or alteration of the function of the nasal passages of the guinea-pig (an obligatory nose breather).
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Bronchiolitis due to the respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in the first year of life. It has been suggested that RSV infection may cause subsequent asthma, but a mechanism for this relationship has not been demonstrated. Studies examining the presence of airway reactivity in infants with RSV bronchiolitis are limited by our inability to administer provocative agents such as histamine to such ill infants. This makes a small animal model of this condition a useful tool in which to investigate the pathophysiology of RSV bronchiolitis. We, therefore, evaluated airway responsiveness in vivo and airway morphometric changes in 20 guinea pigs infected by instilling 4,000 plaque-forming units of human RSV virus onto the nasal mucosa under halothane anaesthesia, while 20 control animals received an equivalent volume of sterile cell culture medium. Six days following instillation, 10 infected animals and 10 controls underwent measurements of pulmonary resistance (RL) following increasing doses of inhaled acetylcholine (Ach). These guinea pigs were then sacrificed and the lung and heart removed en bloc for morphometric studies. There were no differences in baseline RL between infected and control groups. At Ach concentrations of 15 and 50 mg/mL, RSV-infected animals had higher RL values than controls (P < 0.05). Fourteen days following RSV instillation no differences in Ach responses were detected in the 10 infected and 10 control animals studied. To determine whether the increase in airway reactivity 6 days after RSV instillation was associated with changes in airway wall morphometry, 125 airways (69 infected, 56 control) were studied. Analysis of wall area, wall area internal to the smooth muscle, or smooth muscle area standardized by the internal perimeter of the airway showed no significant differences between the infected and control airways. These results demonstrated that airway hyperresponsiveness correlated with previously reported histologic changes of acute bronchiolitis 6 days after guinea pigs were infected with human RSV, but neither hyperresponsiveness nor histological changes persisted following resolution of the primary infection. The increased airway reactivity and the previously observed histological changes seen at day 6 following infection was not due to increased airway wall thickness.
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Pathophysiology
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Abstract Localized recurrent respiratory infections, leading to severe hypoxia in young children without immunological abnormalities or other risk factors, should raise the suspicion of airway structural abnormalities. In a 24‐month‐old boy, with recurrent severe post‐viral wheezing and a history of RSV‐induced bronchiolitis and gastro‐esophageal reflux, fiberoptic bronchoscopy demonstrated an abnormal morphology of the distal portion of the trachea, ending in four openings. Computed tomography (CT) scans demonstrated the presence of a right tracheal bronchus and an anomalous upper lobar bronchus, originating at the level of the major carina. Pediatr Pulmonol. 2009; 44:192–194. © 2009 Wiley‐Liss, Inc.
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Right Main Bronchus
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Inoculation of lambs with an ovine isolate of respiratory syncytial virus (RSV) by a combined intranasal and intratracheal route resulted in mild respiratory tract illness, with respiratory tract lesions. Lung lesions were characterized by bronchitis and bronchiolitis, hyperplasia of bronchial and bronchiolar epithelium, peribronchiolar and perivascular accumulations of lymphocytes, alveolar septal thickening, and collapse. Respiratory syncytial virus was recovered from the respiratory tract of inoculated lambs, and RSV antigen was demonstrated by immunoperoxidase staining of bronchiolar and alveolar epithelial cell in pneumonic lesions of lambs euthanatized on post-inoculation days 5 and 6. Other primary respiratory tract pathogens were not isolated. Clinical signs of respiratory tract illness or respiratory tract lesions did not develop in the in-contact control lamb. Inoculation of the ovine RSV isolate into calves and deer fawns resulted in infection in both species, and at necropsy, pneumonic lesions were present. A mild to moderate respiratory tract illness developed in the calves, but clinical disease was not seen in the fawns. Lung lesions in fawns were similar to those seen in lambs; lesions in calves were characterized by collapse, scattered areas of parenchymal necrosis, and bronchiolitis. Respiratory syncytial virus was reisolated from the lower respiratory tract of inoculated calves and fawns, and immunoperoxidase-positive epithelial cells were seen in pneumonic lesions. Other primary respiratory pathogens were not detected. Respiratory syncytial virus infection was not demonstrable in control animals that were in contact with inoculated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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Tracheitis
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A 10-year-old male domestic shorthair cat died during anesthesia. Grossly, the lungs had multiple nodules corresponding to inflamed airways (bronchitis and bronchiolitis). Microscopically, cuffs and nodular aggregates of lymphocytes and plasma cells surrounded airways. Peribronchiolar fibrosis was also common. Globule leukocytes infiltrated the respiratory epithelium of noninflamed or mildly inflamed bronchi. Argyrophilic and filamentous organisms, consistent with cilia-associated respiratory bacillus-like organisms (CLO), were intermixed with cilia of respiratory epithelium. Ultrastructurally, CLO were longer and thinner than cilia and had a distinct trilaminar membrane, central electron-lucent areas, and no specialized external structures. Silver stained lung sections from 18 additional feline airways revealed similar bacilli in 2/9 normal lungs, 1/7 lungs with bronchitis and bronchiolitis, and 1/2 lungs with pneumonia. The significance of CLO in the pulmonary lesions was not determined.
Respiratory tract
Chronic bronchitis
Atelectasis
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