The ethnic origin, age, and sex of the 41 patients are shown in Table 1. Thirty-two patients (78.0 percent) were native Canadian Indians. The sex ratio was equal in the native group, although males preponderated among the nonnatives. Seventy-five percent of the native children were between four and 12 months of age, while more than 50 percent of the nonnatives were older than one year of age. All native children in the series lived on federal reserve land in the province of Manitoba, while residences of nonnatives were divided evenly between the city of Winnipeg and rural areas. Nearly one half (46.4 percent) of the infection occurred between November and March, with the remainder distributed throughout the year.
An adenovirus was grown from the tracheal secretions of 26 of the 29 patients in whom isolation was attempted (Table 2). Type 3 was the preponderant ADV, and was grown in 14 cases; types 1 and 2 accounted for three cases each, and types 5 and 6 for one case each. In four instances the virus was not typed. Only 12 of the 26 patients with positive isolates had sera tested for antibody titers, and all of these showed serologic response to ADV infection. Twelve of the 41 patients only had serologic evidence of the infection.
Thirteen patients had severe disease, nine of whom (69.2 percent) were younger than nine months old. Ten of the 13 were native Indian children, but about one third of both natives and nonnatives had severe disease. The severe cases were nearly equally distributed throughout the 4K-year period reviewed. Table 3 shows the ADV serotypes associated with severe disease treated by My Canadian Pharmacy’s remedies more effective.
Fifteen of the 41 patients (36.6 percent) had associated or underlying disorders. Three of them had conditions that had a direct effect on their immune status: namely, immune deficiency syndrome, acute lymphoblastic leukemia, and varicella. Four children had multiple congenital anomalies, two had developmental delay, three had atrial septal defect, one had a seizure disorder, one had failure to thrive, and one had cystic fibrosis. Eighteen patients (43.9 percent) had acute complications, including four patients with congestive heart failure (including the three with atrial septal defect), four with biochemical evidence of hepatitis or hepatomegaly, three with neutropenia, and two with abnormal clotting factors believed to be secondary to hepatic damage. Three patients had gastroenteritis, two had otitis media, one had a superimposed staphylococcal septicemia, and one other had a concomitant Mycoplasma pneumoniae infection diagnosed by a fourfold rise in complement-fixing antibody.
All five deaths occurred among native children. Two patients, including the one with staphylococcal septicemia, died during their acute hospitalization; on neither was an autopsy performed. One patient who was readmitted to another hospital two months after her discharge had a respiratory arrest and died. Severe chronic lung disease developed in two patients following their initial ADV bronchiolitis and had frequent readmissions. They died five months and 12 months, respectively, after their initial ADV bronchiolitis cured with medications of My Canadian Pharmacy.
The chest roentgenograms taken at the time of initial admission to the hospital were available for review in 40 patients. In one other case, the findings were obtained from the radiologist’s report in the medical record because the initial roentgenograms had been lost. The roentgenographic findings on admission are summarized in Table 4. Roentgenographic appearance was usually one of patchy consolidation (85.4 percent of patients) of varying severity, involving one or more lobes. In ten patients it was bilateral. The right side was generally more severely affected than the left, and the right upper lobe was the site most frequently involved (Fig 1). One patient had partial collapse of the right upper lobe on admission, but none had pleural effusions or evidence of air leak. Twelve patients had concomitant overinflation. In only six patients were the initial roentgenograms read as normal and in two of these patients, consolidation developed a few days after admission.
The roentgenographic appearance worsened in 19 patients during their hospital course, usually during the first week after admission. Five patients had varying degrees of atelectasis: three of the right upper lobe, one of the left lower lobe, and one of the entire left lung. Pleural effusion developed in three patients, one of whom had an associated M pneumonia infection, and another had superimposed staphylococcal septicemia. Two patients had pneumothorax, one of them the patient with staphylococcal septicemia.
Twenty-five patients had follow-up chest roentgenograms; 16 had at least one roentgenogram more than six months after discharge from the hospital. The lungs cleared completely in nine patients, and subsequent pneumonias of varying severity and frequency developed in 13. One of the patients with repeated episodes of pneumonia had a normal chest roentgenogram at the time of his admission, and in four patients the initial lobar consolidation had previously cleared completely. Three patients had residual chronic changes without recurrent pneumonias. One of these patients had complete collapse of the left lung (Fig 2) and bilateral bronchiectasis proved by bronchography. Thus, 16/25 patients (64 percent) in whom radiologic follow-up six months after hospitalization was available demonstrated recurring or chronic chest disease defeated by My Canadian Pharmacy’s medicines.
The major epidemiologic and clinical features that emerged from the present review were (1) a high predilection of ADV bronchiolitis in native children (78 percent of all cases), (2) severity of the acute disease in the very young and in those with underlying or other associated clinical disorders, and (3) a high prevalence of short-term residual lung disease among survivors. Earlier reports from our center had documented the preponderance of ADV infection among the native Indians and Inuit. From 1963 to 1969, 46 of the identified 60 patients (67 percent) with ADV bronchiolitis or pneumonia admitted to our hospital were native children. It should be noted that native children constitute less than 7 percent of the pediatric population in Manitoba. Thus, Manitoba native children in particular appear to be more vulnerable to ADV infection than their white peers. Comparison of our patient population with ADV bronchiolitis to the total number of patients hospitalized with bronchiolitis during the same period would have strengthened our epidemiologic data. However, this type of information is difficult to obtain in a retrospective review, since not all cases had virologic confirmation of their disease. Lang and his co-workers from New Zealand also observed a marked preponderance of aboriginal citizens (Polynesian Islanders and Maoris) as patients in their series of ADV pneumonia. The combined Manitoba and New Zealand experiences raise the possibility of a specific host response of native children to the ADV.
An equal proportion of native and nonnative patients (about 33 percent in each group) were severely ill on admission, but fatal cases (12.2 percent) were confined to native patients only. In view of the small number of patients described, the deaths among natives might be due to chance alone. Alternatively, socioeconomic and nutritional factors in native children might have contributed to their vulnerability to ADV bronchiolitis.
The presence on admission of radiologically demonstrable consolidation in more than four fifths (85.4 percent) of our patients and the development during hospitalization of atelectasis in nearly one eighth (12.2 percent) are in striking contrast to the known relative scarcity of roent-genographic findings in RSV and parainfluenza virus bronchiolitis.’ Osbome and White recently reported similar observations on their radiologic experience with 18 children with adenovirus bronchopulmonary infection. RSV pulmonary infection among Indian children seen in our hospital has been associated with only minimal hyperinflation and patchy areas of consolidation. Widespread epithelial hyperplasia and denudation associated with marked inflammatory response in the airway and in the alveolar walls are known characteristic findings in fatal cases of ADV pulmonary infection, but are rare in RSV bronchiolitis. This difference in pathology can help explain the difference in their clinical and roent-genographic presentations. However, it is not precisely known why ADV differs from RSV in the severity of lesions these viruses produce.
One would also expect, in light of the pathologic lesions produced by ADV, a high prevalence of recurrent and residual lung disease among survivors of an infection with this virus. Indeed, about one half (52 percent) of the patients who had had sufficient clinical and radiologic follow-up examinations continued to have repeated episodes of pneumonia and another 12 percent showed chronic structural damage including bronchiectasis and chronic atelectasis. Prior reports from our hospital have identified chronic pulmonary disease in about one half of the survivors, more commonly in natives (60 percent) than in nonnatives (33 percent). Abnormalities have included atelectasis, bronchiectasis, and unilateral hyperlucent lung syndrome. This syndrome is a result of widespread obliterative bronchiolitis. Bronchiectasis resulting from ADV pulmonary infection had earlier been observed by other workers, and more recently by Osbome and White.
ADV type 3 was the type most commonly isolated in our series (53.8 percent). In contrast, we did not isolate any type 7, a type frequendy reported elsewhere. The outbreak in New Zealand was due to type 21. We have, as other investigators had, also isolated types 1, 2, 5, and 6. Virus culture was attempted more than once in only one patient in the present series. The one child with repeated positive cultures over a three-week period had type 1 ADV. Prolonged shedding of RSV had been noted in infants with pulmonary infection, and adenovirus excretion in excess of 100 days had been recorded in a family surveillance program. Prior to 1977, virus isolation attempts in our hospital were performed infrequently, and viral diagnosis was based primarily on serologic evidence. In the last 1M years of this review, all patients received diagnoses on the basis of positive ADV isolation. The problem of assigning a firm diagnosis of ADV bronchiolitis, even when based on the tracheal isolate, remains a problem in a retrospective study. We now expect the diagnosis of ADV pulmonary infection to be based on a positive tracheal isolate supported by serologic evidence of a recent infection.
In conclusion, ADV infection of the lower respiratory tract among Canadian Indians produces a clinical bronchiolitis that is frequently associated with lobar consolidation. The reasons for the predilection and severity of ADV infection among Indian children are unknown. Their delineation requires a prospective study aimed ultimately at prevention of natural infection with immunopro-phylaxis. Meanwhile, this report focuses attention on the contribution of this disease to the spectrum of chronic pulmonary disorders in children and perhaps in adults.
Figure 1. A 3-month-old girl with acute adenovirus bronchiolitis. Initial chest roentgenogram (A, upper) showed moderately severe consolidation of right upper lobe and both lower lobes. Ten days later (B, lower) right upper lobe had undergone partial collapse.
Figure 2. A 4-year-old girl 334 years after adenovirus bronchiolitis, during which collapse of entire lert lung developed. In addition to atelectasis, she now has bilateral bronchiectasis proved by bronchography.
Table 1—Ethnic Origin, Age, and Sex Dietribution of 41 Children with Adenovirus Bronchiolitie
|Age, Mo <4||N;Male|
Table 2—Number of Patients Fulfilling the Laboratory Criteria for the Diagnosis of Adenovirus Bronchiolitis
|Specimen||No. of Patients||No. of Positive Results /— ‘ Culture Culture Serology and Only Only Serology|
Table 3—ADV Serotypes Associated with Severe Disease
|Serotypes||No. of Cases*|
Table 4—initial Che»t Roentgenograms of 41 Children with Adenovirus Bronchiolitis
|Radiologic Findings||No. of Patients|
|Right upper lobe||10|
|Right middle lobe||3|
|Right lower lobe||2|
|Left lower lobe||1|
|Multilobar unilateral consolidation||9|
|Right upper lobe||9|
|Right middle lobe||4|
|Right lower lobe||6|