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The etiological, epidemiological and pathogenetical features of bronchiolitis and some clinical and biochemical data concerning seventy nine cases were discussed. It has been underlined the possible pathogenetical role of immunoallergic mechanism (immunoreactions type II, III, IV and VI), and of alterations of humoral immunocompetence (rise of IgM and deficit of IgA). Moreover it has been pointed out that hereditary, socioeconomical and environmental factors could play an important role in determining the seriousness of the clinical picture. The relationship between bronchiolitis and the respiratory diseases of the following years have been examinated.

A retrospective review of children who needed mechanical ventilation for severe bronchiolitis identified 62 cases over a 10 year period. The mean age at initiation of ventilation was 73 days (range: 14-201). Compared with a group of 150 children in hospital for bronchiolitis but not transferred to the intensive care unit, these 62 cases were significantly younger (73.0 compared with 166.3 days), and smaller (4.5 compared with 6.8 kg), and significantly more had been born prematurely (40% compared with 16%). Taken independently, age, weight, and prematurity were significantly associated with the need for artificial ventilation, weight being the most important factor. Using stepwise logistic regression, prematurity in itself added to the quality of the prediction but age did not. The mean duration of mechanical ventilation was 105 hours (range 2-381). Duration of ventilation was significantly longer in children with a low gestational age at birth and a positive familial history of atopy. There were no deaths, and no patient developed pneumothorax or pneumomediastinum. Mechanical ventilation is well tolerated and safe in acute bronchiolitis.

The modes of presentation and the management of acute respiratory failure in 11 infants with severe lower respiratory tract infections (due to respiratory syncytial virus in eight) are described. Progressive respiratory difficulties leading to exhaustion, peripheral circulatory collapse, recurrent apnoeic attacks, or generalized convulsions were the main clinical presentations resulting in severe ventilatory failure. In nine infants preventilation carbon dioxide tensions exceeded 65 mm Hg. It seems likely that the use of intermittent positive-pressure ventilation in these patients contributed to the low mortality rate, less than 0.5%, from such illnesses during the 15-month study period.

The clinical experience of 661 children with bronchiolitis is reported in four-years period to gain a better understanding of diagnosis and pathogenesis of bronchiolitis. Upper airways infections, expiratory dyspnea, clear sound by chest percussion, vesicular rales and whistling by chest auscultation, air trapping on the chest radiography were considered as essential data of diagnosis. It was found in 595 patients: expiratory dyspnea, air trapping, vesicular r. and whistling in 85% and whistling only in 15%; hypoxemia in 20% combined with hypercapnic acidosis in 10%; normoxemia in 80% combined with hypocapnia in 54%; hyperlactemia in 64% combined with an increment in the serum of CPK in 50% and of GPT in 30%; virus were cultured in 27%, adenovirus and RSV were identified in 90%. Instead it was found in 66 patients: air trapping but no difficult breath, with normal chest auscultation; crisis of cyanosis or paleness-cyanosis chilly sweat in 80% were motive of admission. The clinical and/or radiological features of "air trapping" were considered as essential symptoms and signs of bronchiolitis. The insufficient systemic perfusion was considered as a frequent occurrence and as cause for sudden respiratory and circulatory emergency.

Three- to 4-hour polygraphic sleep studies were carried out in 16 infants aged between 1 and 6 months during and after recovery from acute bronchiolitis. During bronchiolitis 35% of total sleep time was active sleep compared with 31% after recovery. Respiration rate was increased during bronchiolitis and was higher in active sleep and quiet sleep irrespective of the stage of the illness. Apnoeic pauses were invariably shorter than 15 seconds, the mean duration for active sleep and quiet sleep being similar during infection and after recovery. Apnoeic episodes were central in type and generally initiated by a sign or body movements. Preapnoea heart rate was significantly higher than during or after apnoea. Apnoea index (the percentage of time the baby spends apnoeic), apnoea attack rate (the number of episodes of apnoea per unit time), and apnoea percentage (the distribution of episodes of apnoea while in a given sleep state) were increased significantly in quiet sleep during the index illness. Transcutaneous oxygen tension was significantly reduced during the course of infection, but comparable values were obtained in active sleep and quiet sleep during initial and recovery periods. These results show that the main changes in respiration pattern during the course of acute bronchiolitis occur in quiet sleep.

The very high incidence of ME pathology in epidemic bronchiolitis prompted the systematic use of impedance measurement tests in a study of the otitic process. Data were assembled of 44 children admitted to the paediatric clinic with acute viral respiratory infection (in the last year). On account of the high incidence (97%), the precocity of occurrence (1-12 months), the slow rehabilitation and the frequency of relapses, the ME pathology in these children indicates the importance of a correct approach to the problems of relapsing otitis in infants. Patients were treated with aerosol therapy (mucolytic substance), nasal drops (with vasoconstrictors), and only in very serious cases with antibiotics. For the latter, cortisonic therapy is inadvisable, while it is absolutely necessary to follow up with periodic controls until the tympanogram becomes normal. The impedance findings (prevalent type B curves, with inability to evoke the stapedius reflex, over periods of several months) and their resolution in type AC or C curves led us to consider not only the organic problem, but also the functional hearing problem during the first year of life, and the possible longterm repercussion.

Lower respiratory tract infections in children, including group, bronchiolitis, and bronchitis are frequently associated with recurrent episodes of wheezing. Different respiratory viruses assume greater importance at different ages of children. Respiratory syncytial virus is the most prevalent viral respiratory infection in preschool children, while rhinovirus is of increasing importance in older children. Asymptomatic virus shedding and mild respiratory infections do not provoke asthma symptoms nor do bacteria, except in association with sinusitis. Furthermore, epidemiologic studies strongly suggest that viral lower respiratory tract illness in early childhood is associated with pulmonary abnormalities, including bronchial hyperreactivity and peripheral airway obstruction that may persist for many years, and is possibly a cause of chronic airway obstruction in adulthood. Several different mechanisms have been identified by which respiratory viruses provoke asthma. No one single mechanism, however, adequately explains virus-induced asthma. Nonetheless, a common thread to these various proposed mechanisms is the ability of respiratory viruses to cause airway inflammation, either directly, through cytopathic effects, or indirectly, by increasing the inflammatory processes of respiratory cells. The consequence of these effects causes increased airway responsiveness and asthma.

Fifty-one infants admitted to hospital because of acute bronchiolitis were followed until 2 years of age. Sixty per cent had three or more attacks of bronchopulmonary obstruction, and the remainder two or less attacks. The children with three or more attacks also had more respiratory infections. They had younger parents and their close relatives more often had respiratory atopic illness. The children with three or more attacks wheezed for a longer time after the bronchiolitis. No difference was found for breast-feeding, neonatal respiratory complications, crowded homes, parental smoking and other social factors. To detect children at risk of recurrent obstructive airways disease after bronchiolitis, a discriminant analysis was performed. The discriminant function classified 28 of the 31 children with recurrent obstructive episodes as belonging to the risk group, and 18 of the 20 children with two or less episodes to the non-risk group.

Acute bronchiolitis in infancy appears to be associated with persistence of wheezing or subsequent asthma in later life. Chest imaging techniques have demonstrated persistent structural lung damage such as atelectasis, bronchiectasis, and obliterative bronchiolitis among survivors of the more severe forms of bronchiolitis. In addition, in a significant number of survivors without demonstrable structural damage, pulmonary function studies have revealed a spectrum of disturbances including air-trapping, reduced air flow at low lung volumes, hypoxemia (all indicating disease in the small airways), and bronchial hyperreactivity. However, it has not yet been proven definitively whether the relationship between severe bronchiolitis in infancy and chronic obstructive lung disease is causal or noncausal. Further prospective clinical studies are needed to resolve this question.

The distinction between congenital or acquired lung disease is often a difficult problem. This is illustrated by case reports on two boys aged 10 and 12. The clinical, pulmonary function and radiological details were very similar in the two cases, suggesting pulmonary hypoplasia. However, the histology seen in the second case, a type of bronchiolitis obliterans and follicular bronchiectasis were among several arguments in favour of acquired pulmonary disease of infective origin. The recorded literature as well as this observation show that certain respiratory viral infections may lead to bronchial and above all bronchiolar damage which can be severe and progressive.

This study investigated histamine concentration in nasal secretions from children who had viral respiratory tract infection. It demonstrated that (1) there may be appreciable histamine in nasal secretions during viral respiratory tract infection; (2) concentration of histamine in serum may be elevated at the same time; and (3) children with past medical or family history of atopy had more histamine in nasal secretions during viral infections than did nonatopic children.

Four infants in whom excessive secretion of antidiuretic hormone was associated with pulmonary infections are reported. Severe hyponatraemia was noted in 3 of them; in the fourth, fluid restriction may have prevented this complication.

Inspiratory or exspiratory stridor associated with dyspnea represents a common pediatric symptomatology compatible with various diseases which usually are of infectious etiology. The causative obstruction of the infantile airways may lead to life-threatening respiratory failure. A review is conducted of the most important emergencies characterized by stridor and dyspnea in early childhood: croup syndromes (acute viral laryngotracheitis, spasmodic croup, bacterial tracheitis), epiglottitis and bronchiolitis.

Bronchial hyperreactivity is a common report in several respiratory tract diseases such as bronchial asthma, chronic bronchitis and cystic fibrosis. Atopic patients and children who suffered lung diseases in early life (laryngotracheobronchitis, bronchiolitis, bronchopulmonary dysplasia) may have also persistent abnormalities in pulmonary function that frequently include bronchial hyperreactivity. A review of the actual literature, specially concerning with the clinical aspects of bronchial hyperreactivity in children and with the possible etiopathogenetic mechanism is presented.

The action of a medicinal spray that contains anti-inflammatory and bacterio-static drugs integrated with the penetrating and potentiating agent DMSO has been evaluated clinically in 60 infants with acute respiratory obstruction. A dose of 2 ml of this spray is applied in the posterior pharynx and the tonsil region; 1 to 4 applications are made, according to the clinical evolution of the case. Two groups were chosen at random; 60 patients were paired off, and one of each pair received the treatment with DMSO spray. All the patients received ampicillin (50-100 mg/kg body weight). The following clinical results were observed. First there was an immediate recovery, after an average lapse of 30 min; improvement of sensorial involvement was observed in 80% of the cases, reduction of the intercostal retraction in 75%, reduction of polypnea in 76%, and transformation of the obstructive syndrome into a catarrhal syndrome in 80% (with fluidification of the secretions, which were expelled more easily by the upper air tracts). There was also a deferred or maintenance effect, which evaluated in comparsion with the control group that received similar treatment except for the nebulizations with DMSO spray. A sequential design, based on whether or not it was necessary to use the croupette, demonstrated the superiority of the DMSO spray over the control treatment in the bronchiolar process; in the group treated with DMSO spray it was not necessary to use the croupette. The sequential design based on the effect of this therapy on the general condition and the tabulated clinical factors permitted the inference that the therapeutic responses are more favorable in the group treated with DMSO spray than in the control group. In the sequential design, the line of significance is cut at the fifteenth pair (an error of 0.05 and P equals 0.95%). Since the application is easy, there are no toxic side effects and in view of the favorable results in the clinical evolution of the acute respiratory obstructive processes, we consider the use of this therapeutic spray very useful and beneficial in bronchiolitis.

Lung function was measured in nine infants, ages 15-36 weeks, who had persistent wheezing, apparently following acute bronchiolitis, before and after 2 weeks of treatment with either inhaled nebulized beclomethasone dipropionate (BDP) or placebo in a randomized, double blind, crossover trial. The effect of nebulized albuterol (Salbutamol) was measured before and after the steroid treatment. Thoracic gas volume (TGV) and specific airway conductance (SGaw) were determined using a whole body plethysmograph, and forced expiratory flow at resting lung volume (VmaxFRC) was determined with a thoracoabdominal compression jacket. All infants had marked airways obstruction before treatment with mean +/- SE VmaxFRC of 24 +/- 4% predicted and SGaw of 37 +/- 5% predicted. Two weeks of placebo treatment had no significant effect on lung function, but after 2 weeks of BDP inhalation there was a significant rise in SGaw to 61 +/- 7% (P less than 0.005). VmaxFRC increased to 42 +/- 13% but the difference did not reach significance. Respiratory rate and clinical score for retractions and wheezing also fell significantly with BDP therapy (P less than 0.01 and P less than 0.001 respectively). Albuterol had no effect on lung function either before or during steroid therapy. Steroids may have a role in the management of persistent wheezing following bronchiolitis.

Twenty-three children less than 18 months old who had clinical and radiological evidence of bronchiolitis and remained symptom-free thereafter were studied to determine pulmonary function ten years later. Abnormal Pao2, Viso V and RV/TLC ratio were found in the majority of subjects, and 31.3% had abnormalities in all three tests; four and one-half percent had exercise-induced bronchospasm. These changes indicate a residual parenchymal or airways lesion following bronchiolitis.

A historical cohort study was performed in order to assess the hypothesis that even mild bronchiolitis in infancy in a predictor of wheezing later in childhood. Subjects who had experienced bronchiolitis and a matched control group were compared in terms of reported wheezing 8 years later. A highly significant difference was found between the bronchiolitis group and the control group in terms of current wheezing (P less than .0001, relative risk 3.24). This difference was maintained after adjusting for many potentially confounding variables including family history of allergy and other allergic manifestations in the child. Results suggested that 13.6% of a normal practice population in the age range 6 to 9 years currently wheeze, but that 44.1% of children who experienced bronchiolitis currently wheeze. Based on the incidence of bronchiolitis (4.27/100 children in their first 2 years of life) and the relative odds for wheezing derived from a logistic regression model including variables that measured passive smoking, genetic tendency to wheeze, and bronchiolitis, calculations of attributable risk suggested that wheezing in 9.4% of the population of children who currently wheeze was attributable to bronchiolitis.

We reviewed our experience with 41 children hospitalized from 1974 to 1978 for adenovirus (ADV) bronchiolitis. Thirty-two patients (78 percent) were native Indians between four and 12 months old. In 18 of the 41 patients (43.9 percent) acute complications developed. The five fatal cases (12.2 percent) were confined to native children. The initial chest roentgenograms showed lobar consolidation in 35 patients (85.4 percent). Atelectasis developed in five (12.2 percent) during hospitalization. Sixteen of 25 patients (64 percent) with adequate radiologic follow-up examination had subsequent pneumonias or showed residual chronic changes. The reasons for the predilection of ADV bronchiolitis in native Indian children and the precise effect on subsequent airway function in survivors are unknown and require further study. We emphasize the importance of ADV as a cause of bronchiolitis in native Indian children. Furthermore, this report focuses attention on the contribution of this disease to the spectrum of chronic pulmonary disorders in the pediatric group.

Severe respiratory disease associated with bovine respiratory syncytial virus (BRSV) infection has been identified in dairy cattle in New York State. The cases identified occurred in dairy calves and heifers. The disease was characterized in 4 animals by pathologic changes including interstitial pneumonia, necrotizing bronchiolitis with multinucleated syncytial epithelial cells and interstitial emphysema. BRSV antigen was demonstrated in lung samples or was isolated in tissue culture in all 4 cases. A retrospective survey of 6279 bovine diagnostic accessions between 1977 and 1982 revealed 66 cases of interstitial pneumonia, often with concurrent bronchiolitis. In this 5 year period, only 1 case in 1981 had interstitial pneumonia and bronchiolitis with pathologic features consistent with BRSV infection. It is concluded that pathogenic BRSV has entered New York State and that it is contributing to clinical respiratory disease in dairy cattle.

We assessed the clinical progress of 55 children 2 years after admission to hospital with acute bronchiolitis and performed lung function tests on 40. During the 2 year follow up period 75% of the children had wheezed, 36% had 2 or more lower respiratory symptoms lasting more than 2 weeks, 33% had more than 100 days of lower respiratory symptoms, and 13% were readmitted to hospital with acute respiratory disease. In addition 60% of the children were hyperinflated on lung function tests. Many of the children with hyperinflation at the 2 year assessment had not been hyperinflated 1 year earlier, suggesting variable airways obstruction. Reversibility of airways obstruction was also assessed by response to nebulised salbutamol. Nine children had a fall greater than 15% in airways resistance after salbutamol and these children had the highest baseline airways resistances. Airways resistance was higher in the children with a family history of atopy.

To determine whether the magnitude of the respiratory syncytial virus (RSV)-specific IgE response at the time of an episode of RSV bronchiolitis in infancy accurately predicts the development of subsequent wheezing episodes, we observed 38 infants prospectively from the time of an episode of infantile bronchiolitis through 48 months of age. Peak RSV-IgE titers were measured at the time of the bronchiolitis episode using an ELISA procedure. Notation was made of both the number of subsequent wheezing episodes reported by parents and the number documented by a physician. Subsequent wheezing was documented by a physician in 20% of infants who did not develop an RSV-IgE response at the time of the bronchiolitis episode and in 70% of those with the highest responses (P less than 0.025). These results suggest that the magnitude of the RSV-IgE response at the time of RSV bronchiolitis is a useful prognostic indicator for recurrent wheezing.

A historical cohort study was conducted to measure lower respiratory tract illness (LRTI) up to nine years following mild bronchiolitis and to discover attributes that predict an increased risk for LRTI in childhood. The hypothesis assessed was that the occurrence of bronchiolitis predicts LRTI following the second birthday (childhood LRTI) after adjusting for potentially confounding variables such as a family history of respiratory allergy. Fifty-three children (index subjects) who were seen for bronchiolitis at a suburban community pediatric practice were compared on the basis of childhood LRTI with a control group of 159 children. Chart review, when children were a mean of 8 years old, determined the frequency of childhood LRTI. The mean frequency of childhood LRTI was greater in index subjects than in control subjects (1.62 vs 0.98). This difference remained after adjusting for potentially confounding variables. The yearly occurrence of any LRTI was significantly more common in index subjects through the third year of life (38% vs 15%). A tendency for a more common occurrence of any LRTI was noted through the fifth year (25% vs 16%), but not thereafter. Further analysis of index subjects disclosed that only those who experienced a subsequent LRTI before the second birthday were at an increased risk for the development of childhood LRTI.

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.

Spontaneous pneumothorax is an uncommon complication of bronchiolitis due to respiratory syncytial virus. Bilateral spontaneous pneumothorax in an infant with respiratory syncytial virus bronchiolitis has not been previously reported. We report the case of a four-month-old infant who presented in respiratory distress owing to respiratory syncytial virus bronchiolitis with bilateral pneumothoraces. The infant improved with evacuation of air from the chest.

A 4-year-old girl who had received a fetal thymus gland by intraperitoneal transplantation 41 months previously sustained acute, fatal bronchiolitis due to culture-proven cytomegalovirus despite the fact that a specific antibody response to this organism was detected. While the thymic transplantation had increased the number of circulating T lymphocytes and had permitted immune sensitization to delayed-hypersensitivity skin test antigens, there was still an incomplete state of T lymphocyte function. In particular, isolated lymphocytes failed to respond to stimulation with phytohemagglutinin at several concentrations and, more important, the pathologic examination demonstrated a severe anatomic deficiency of lymphoid tissue associated with T lymphocyte function. The unusual infection that caused the death of this child emphasized the necessity of acquiring sufficient T lymphocyte function in immunologic reconstitution attempts.

Airway reactivity and the effects of bronchodilators in infants are controversial. We studied the response to bronchodilator treatment in 14 mechanically ventilated infants (mean age, 2.74 months; range, 0.6-5.9) in respiratory failure caused by respiratory syncytial virus (RSV)-associated bronchiolitis. Sixteen infants without lung disease, undergoing elective surgery, provided normal values. Maximum expiratory deflation flow-volume (DFV) curves were produced by manual inflation of the lungs with an anesthesia bag to a predetermined static airway pressure followed by rapid deflation with a negative airway pressure before and after administration of bronchodilator. At baseline, the bronchiolitis group had a forced vital capacity (FVC) of 34.5 +/- 3.6 ml/kg compared with 41.8 +/- 1.5 ml/kg in the normal group; maximum expiratory flow rate at 25% of FVC (MEF25) was 10.2 +/- 2.0 ml/kg/s compared with 27.3 +/- 2.0 ml/kg/s in the normal group. The clinical and radiologic impression was severe lower airway obstruction and air trapping. After administration of bronchodilator, FVC did not increase significantly, but MEF25isov increased by over 30% in 13 of 14 infants. Mean MEF25 increased by 148 +/- 43.2% to 21.7 +/- 3.9 ml/kg/s (P less than 0.02). These findings indicate that during the acute phase of severe RSV-positive bronchiolitis most infants have airway reactivity that responds positively to bronchodilator treatment.