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Biomedical subjects

W A Clyde

Publications and source records attributed to W A Clyde.

At least 37 records · Page 2Linked to original sources

A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion.

We analyzed data from a 14-year longitudinal study of respiratory infections in young children to determine the relative importance of viral respiratory infection and nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae as factors influencing the occurrence of acute otitis media with effusion. The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P less than 0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk; 1.5; P less than 0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease. Prevention of selected otitis-associated viral infections should reduce the incidence of this disease.

Acute Disease↗

Mycoplasma pneumoniae infection: role of a surface protein in the attachment organelle.

Attachment of Mycoplasma pneumoniae to host cell by means of a specialized terminus initiates infection. Monoclonal antibodies to a surface protein (Pl) inhibit this process, and react with a region of the tip covered with peplomer-like particles. Since antibodies against the Pl protein are generated by natural and experimental infection and by immunization, the substance may be an important determinant of protective immunity.

Bacterial Proteins↗

Pneumonia: an eleven-year study in a pediatric practice.

Data from an 11-year study of acute lower respiratory tract illness were analyzed to provide added insight into the causes and patterns of occurrence of pneumonia in an outpatient pediatric population. Over 80% of all episodes of pneumonia occurred in children less than seven years of age; the peak attack rate was observed in 2-4-year-old children. A virus or Mycoplasma pneumoniae was isolated from 24% of children with pneumonia; 57% of all episodes occurred during outbreaks for which a viral or mycoplasmal cause could usually be identified. Respiratory syncytial virus (RSV), parainfluenza viruses types 1 and 3, adenoviruses, influenza A viruses and M. pneumoniae accounted for 86% of all isolates. Attack rates of pneumonia in preschool children were highest during periods of RSV and influenza A virus prevalence; M. pneumoniae was the most frequent isolate from school aged children. The data contained in this report augment the understanding of the causes of pneumonia in children and provide a data base for scientists interested in the prevention of lower respiratory tract illness in children.

Adolescent↗

The epidemiology of tracheobronchitis in pediatric practice.

Epidemiologic characteristics of childhood tracheobronchitis occurring over a 104-month period in Chapel Hill, NC, were ascertained and compared to those of other pediatric lower respiratory illness (LRI) syndromes. Tracheobronchitis accounted for 40% of all LRI seen at the community's only pediatric practice. Tracheobronchitis incidence was highest during the first two years of life, through the ratio of tracheobronchitis incidence to total LRI incidence increased with age. A viral pathogen or Mycoplasma pneumoniae was isolated from 23% of tracheobronchitis cases; the agents most commonly isolated were parainfluenza viruses, influenza viruses, respiratory syncytial virus, and M. pneumoniae. Influenza virus, particularly type B, was isolated more commonly in tracheobronchitis than in other LRI syndromes. Over all age groups, peak incidence of tracheobronchitis, like that of pneumonia and bronchiolitis, occurred during the winter months. In school-age children, however, tracheobronchitis incidence was more likely than that of other syndromes to be elevated in late winter or early spring, when several influenza B outbreaks occurred in Chapel Hill. Available evidence suggests that risk of chronic respiratory disease is related inversely to age at which acute respiratory infection first occurs, and that a component of wheezing may not be required to confer such risk. These considerations, coupled with the high incidence of tracheobronchitis early in life, warrant further description of this syndrome and assessment of its implications.

Age Factors↗

Characterization of hemadsorption-negative mutants of Mycoplasma pneumoniae.

Previously isolated mutants of Mycoplasma pneumoniae incapable of hemadsorption were characterized with respect to specific protein content, tracheal ring attachment capability, and virulence for both in vitro and in vivo model systems. Two-dimensional gel electrophoresis revealed both quantitative and qualitative differences between the protein complements of two different mutant strains and that of the virulent parent strain. Studies of mycoplasma attachment to hamster tracheal rings in vitro demonstrated that only one of these mutant strains still possessed the ability to attach to the respiratory epithelium via neuraminidase-sensitive receptors. Measurement of [3H]orotic acid uptake in mycoplasma-infected tracheal rings indicated that infection with the hemadsorption-negative mutants resulted in only slight reductions of ribonucleic acid synthesis, similar to levels observed for tracheal rings infected with an avirulent strain of M. pneumoniae. The virulence potential of the two mutant strains was further investigated by utilizing the hamster model system. Both mutant strains were rapidly cleared from the lungs of infected animals and produced little or no microscopic pneumonia.

Animals↗

The cotton rat as an experimental model of human parainfluenza virus type 3 disease.

Intranasal or aerosol inoculation of cotton rats (Sigmodon hispidus) with human parainfluenza virus type 3 (P3) produces pulmonary changes which closely resemble human disease due to this agent. Active viral replication resulted in peak titers by day 2 of infection. Viral antigen was localized by immunofluorescence in bronchial epithelial cells alone (aerosol inoculation) or epithelial and alveolar cells (intranasal instillation). Cytopathic effects in epithelial cells was noted as early as day 2, and marked cellular proliferation occurred by day 7. Intranasal instillation of virus resulted in development of patchy interstitial pneumonitis. Mononuclear cell infiltration in the peribronchial and perivascular areas peaked on days 6 and 7. A brisk systemic antibody response was measured both by complement fixation and virus neutralization techniques. These data establish the value of the cotton rat as an experimental model for the study of bronchiolitis and pneumonia due to P3. Since previous work has demonstrated that respiratory syncytial virus and Mycoplasma pneumoniae also will replicate and cause pulmonary disease in cotton rats, comparative studies in a single animal species are facilitated.

Animals↗

Serum IgE levels and the clinical expression of respiratory illnesses.

The incidence, clinical manifestations, and infectious etiology of respiratory illnesses observed in a prospective longitudinal study were correlated with serum IgE values, which were used as objective markers of atopy. The incidence of wheezing illnesses was greater in children with elevated IgE levels, confirming an association previously reported. In contrast, the incidence of upper respiratory illness or middle ear disease showed no correlation with IgE values. The number and types of viral infections distributed evenly throughout the population. The results suggest that children with recurrent URI or MED deserve evaluation for allergy only if there are other clinical findings suggestive of atopy.

Bronchial Spasm↗

Dynamic respiratory mechanics in intact anesthetized hamsters.

A system for measuring parameters of ventilation and respiratory mechanics in intact anesthetized hamsters was developed. Means +/- SD of five weekly measurements in eight hamsters were 0.68 +/- 0.09 ml for tidal volume, 45 +/- 14 breaths.min-1 for respiratory frequency, 29.3 +/- 10.4 ml.min-1 for minute ventilation, 0.301 +/- 0.080 ml.cmH2O-1 for dynamic compliance, 0.435 +/- 0.151 cmH2O.ml-1.s for inspiratory resistance, 0.311 +/- 0.101 cmH2O.ml-1.s for expiratory resistance, and 0.334 +/- 0.096 cmH2O.ml-1.s for average resistance. The standard deviations of five consecutive measurements of these parameters on the same day were typically 10% of the corresponding mean values suggesting that acute changes as small as 10% can be detected in a study of similar size. The corresponding value for five single measurements on different days at weekly intervals was 30%. We believe that this system yields reasonable and repeatable measurements, and, because it is atraumatic, it can be used in chronic studies of diseases in hamsters and other small animals.

Airway Resistance↗

Experimental models for study of common respiratory viruses.

Numerous epidemiological studies have shown that there is excess respiratory disease morbidity in areas of high atmospheric pollution, implying an interactive effect on the clinical illness associated with these common infections. The principal etiologic agents of human respiratory infections are respiratory syncytial virus (RSV), influenza viruses (IV), parainfluenza virus types 1 and 3 (P1, P3), adenoviruses (AD), rhinoviruses (RV) and Mycoplasma pneumoniae (Mpn). Understanding the pathogenesis of the excess morbidity related to pollutants would facilitate detection of undesirable human health effects and provide a basis for intervention strategies. Through use of experimental model systems the mechanism of toxic effects could be defined (whether microbiological, immunological, pathological or physiological) to provide direction for appropriate studies in the human host. Small animal models of IV and Mpn infections have been available for many years; recently, experimental models of several more common viral diseases have been developed. A parallel to human RSV infections is provided by the ferret: virus replicates in the lungs of infant animals, but only in the noses of adults. The common cotton rat infected with RSV develops small airways lesions which may mimic the pathophysiologic changes of bronchiolitis. Both guinea pigs and Syrian hamsters are susceptible to human P3 virus, developing peribronchiolar and interstitial lesions. Practical small animal models for human AD and RV infections are not available because of the high host-specificity of these agents. Both the RSV and P3 model infections are nonlethal which enables study for long-term sequelae. Recent reports of pulmonary function abnormalities among children suffering bronchiolitis in infancy underscores the importance of defining toxic influences which could play a role by making the initial infections more severe.

Adenoviridae Infections↗

Ciliary membrane alterations occurring in experimental Mycoplasma pneumoniae infection.

Experimental infection of hamster ciliated tracheal epithelium in organ culture with virulent Mycoplasma pneumoniae resulted in the deterioration o ciliary necklaces and an altered distribution of membrane-associated particles on the shafts of the affected cilia. To our knowledge that is the first report of an altered disposition of ciliary membrane-associated particles in response to a specific infectious agent.

Animals↗

Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children.

To better understand acquired immunity to respiratory-syncytial-virus infections, we analyzed data from a 10-year study of respiratory illness in normal children who were followed longitudinally from early infancy. Immunity was measured in terms of failure to become infected or reduction in severity of clinical illness upon reinfection. Outbreaks of infections occurred seven times over the 10-year-period. During epidemics the attack rate for first infection was 98 per cent. The rate for second infections (75 per cent) was modestly reduced (P less than 0.001); that for third infections was 65 per cent. Age and history of infection both influenced illness. Immunity induced by a single infection had no demonstrable effect on illness associated with reinfection one year later; however, a considerable reduction in severity occurred with the third infection. These observations suggest that amelioration of illness--rather than prevention of infection--may be a realistic goal for immunoprophylaxis.

Antibodies, Viral↗

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice.

To develop a broad understanding of the causes and patterns of occurrence of wheezing associated respiratory infections, we analyzed data from an 11-year study of acute lower respiratory illness in a pediatric practice. Although half of the WARI occurred in children less than 2 years of age, wheezing continued to be observed in 19% of children greater than 9 years of age who had lower respiratory illness. Males experienced LRI 1.25 times more often than did females; the relative risk of males for WARI was 1.35. A nonbacterial pathogen was recovered from 21% of patients with WARI; respiratory syncytial virus, parainfluenza virus types 1 and 3, adenoviruses, and Mycoplasma pneumoniae accounted for 81% of the isolates. Patient age influenced the pattern of recovery of these agents. The most common cause of WARI in children under 5 years of age was RSV whereas Mycoplasma pneumoniae was the most frequent isolate from school age children with wheezing illness. The data expand our understanding of the causes of WARI and are useful to diagnosticians and to researchers interested in the control of lower respiratory disease.

Adolescent↗

Spirometric changes in normal children with upper respiratory infections.

Recent evidence that certain uncomplicated upper respiratory infections induce pulmonary function abnormalities in adults prompted a prospective study in children, in whom such infections occur more frequently. In a longitudinal study, 55 children 2.5 to 11 years of age were observed for a mean duration of 2 years. Spirometry and lung volume studies were obtained routinely every 3 months, during each upper respiratory infection, and 4 weeks after illnes, providing data for 617 "well" and 237 "illness" observations. After grouping of data by sex and age (less than 84 of greater than 84 months), each spirometric parameter was analyzed using linear regression with individual identification, height, and clinical status (normal versus upper respiratory illness) as independent variables. Adjusted mean values of forced vital capacity, 1-sec forced expiratory volume, peak expiratory flow, maximal mid-expiratory flow, and expiratory flow at 50 per cent of the forced vital capacity all decreased during upper respiratory illness. The data suggest that lower respiratory tract involvement without signs or symptoms of lower airway or alveolar disease occurs with upper respiratory illnesses of varied etiologic origin in childhood.

Body Height↗

The epidemiology of bronchiolitis.

From the data presented a composite epidemiologic picture of bronchiolitis can be drawn. If one uses a large brush the picture would be that of a common, mild disease during the first 2 years of life, due primarily to RSV and occurring predominantly in males during the winter and spring months. If the drawing is examined more closely, however, a more complex picture is seen. Our data suggest that this syndrome is very common indeed if children are followed closely and examined carefully, but under these circumstances is quite mild. If more strict criteria, such as hospitalization, are applied for inclusion of patients with bronchiolitis a different age distribution is seen. Most children who become severely ill are under 6 months of age and in this group morbidity and mortality are high. Agents other than RSV cause bronchiolitis but in these instances the age occurrence and seasonal occurrence are different from those seen with RSV disease. The predominance of bronchiolitis in males is striking. Our day care center data suggest that mild bronchiolitis occurs with equal sex frequency. This would suggest that the reason more boys are carried to the pediatrician or hospitalized is because they get sicker. Further studies on this phenomenon are in progress. Finally, our data suggest that many bronchiolitis cases from whom no agents were isolated were due to RSV. There is, however, a segment of bronchiolitis cases that occurs in the young child during all seasons which suggests that the young bronchiole may react to a variety of stimuli. This poses a real problem for the investigator of bronchiolitis; hopefully meaningful answers will be available soon.

Age Factors↗