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The use of albuterol in hospitalized infants with bronchiolitis.

OBJECTIVES: To determine whether the use of albuterol by nebulization enhances physiologic or clinical recovery in hospitalized infants with moderate bronchiolitis. METHODS: This prospective, double-blind, placebo-controlled, randomized clinical trial was performed from December 1995 to March 1996. A total of 52 patients <24 months of age with a diagnosis of moderately severe, acute viral bronchiolitis were enrolled and assigned to receive nebulized albuterol or normal saline placebo for 72 hours under a standardized protocol. Primary outcome measures included improvement in oxygen saturation (SaO2) during hospitalization and survival analysis to assess the time required to reach preestablished discharge criteria on three measures: SaO2, accessory muscle use, and wheezing. An additional secondary outcome measure was actual length of hospital stay. Adverse outcomes also were compared between treatment groups. RESULTS: There was no significant difference in mean SaO2 between albuterol and placebo at baseline, 24 hours, or maximum SaO2 achieved during hospitalization. Both groups showed significant improvement in oxygen saturation over time, but there was no significant difference in improvement between the two groups. The study had a power of 90% to detect a difference in mean percentage point improvement of 2% SaO2. There was no difference in time to reach discharge criteria as defined by SaO2, accessory muscle use, or wheezing. There was no difference in length of hospital stay or in the frequency of adverse outcomes. CONCLUSIONS: Nebulized albuterol therapy does not appear to enhance recovery or attenuate severity of illness in infants hospitalized with acute, moderate bronchiolitis, as evidenced by improvement in oxygen saturation, time to meet standardized discharge criteria, or length of hospital stay.

Adrenergic beta-Agonists↗

Assessment of bronchodilator responsiveness in infants with bronchiolitis. A comparison of the tidal and the raised volume rapid thoracoabdominal compression technique.

Whether bronchodilators should be used for the treatment of infants with bronchiolitis is subject to debate, partly because of the low sensitivity of the methods for assessing lung function changes in infants. In the present study, we compared the recently introduced raised volume (RVRTC) with the conventional end-tidal rapid thoracoabdominal compression (ETRTC) technique in infants with acute viral bronchiolitis. In 17 infants lung function was assessed by both methods, at baseline values and after salbutamol inhalation. Forced expiratory volumes (FEV(0.5), FEV(0.75), FEV(1.0)) were used for the quantification of RVRTC measurement, and maximal expiratory flow at functional residual capacity (Vmax (FRC)) for ETRTC measurements. A significant individual change was defined by a mean postbronchodilator value that differed from baseline value by more than twice the within-subject coefficient of variation (CV). Group mean intrasubject CVs ranged from 4.7% to 5.3% for FEV parameters; it was 14.0% for Vmax (FRC). For the group, post-bronchodilator measurements did not differ significantly from baseline measurements. For the majority of infants, however, the within-subject comparison of responses revealed substantial differences between both techniques; while no infant demonstrated a significant increase in Vmax (FRC), eight (47%) infants responded with significantly improved timed volumes. The RVRTC technique provides the investigator with a more sensitive diagnostic tool for documenting the effectiveness of therapeutic interventions on an individual basis. Furthermore, the findings of the present study provide a rationale for the application of bronchodilators in a subgroup of infants with acute bronchiolitis.

Administration, Inhalation↗

Experimental reovirus serotype 1/strain Lang infection of the lung: a model for the study of the lung in the context of mucosal immunity.

A number of studies have examined the nature of the respiratory immune response to particular pathogens. Although many pathogens stimulate specific immunity in the lung, they frequently are not effective immunogens at other mucosal sites. Because the gastrointestinal tract is a major inductive site for mucosal immunity, a pathogen that is an effective respiratory and gut immunogen would allow studies of the interaction of the lung with gut mucosal immune system. Reovirus, a respiratory isolate that previously has been shown to be an effective gut mucosal immunogen, provides a potential model of the relationship of the lung to the gut mucosal immune system. In this report, we demonstrate that intranasal application of reovirus serotype 1/strain Lang (1/L) to CD-1 mice elicits an acute lymphocytic inflammatory infiltration of the lung and hyperplasia of the lung-associated lymph nodes. The initial inflammatory response occurs in the airspaces and interstitium of the lung. As the infection progresses, the initially diffuse cellular infiltrate becomes more focused around small bronchioles. Viral replication occurs predominantly during the first week of the infection, and infectious virions are eliminated during the second week. After the elimination of infectious virions, a secondary response consisting of the appearance of plasma cells adjacent to pulmonary arteries develops as the primary infiltrate organizes into peribronchiolar follicles, resembling the human inflammatory lung condition termed follicular bronchiolitis. These two infiltration patterns were also observed by immunohistochemical analysis of the the infected lung. Whereas CD4+ and CD8+ lymphocytes and Mac-1+ cells were found to be more closely associated with the primary infiltration process, B220+ lymphocytes were observed adjacent to pulmonary arteries. These results establish respiratory reovirus 1/L infection as a viable model for future investigations of the mucosal immune response in the lung and its relationship to the common mucosal immune system.

Animals↗

The potential impact of prophylaxis against bronchiolitis due to the respiratory syncytial virus in children with congenital cardiac malformations.

AIMS: To determine the number of infants in the Mersey and North West regions with congenital cardiac disease for whom palivizumab may be appropriate, and to examine the potential impact of introducing prophylaxis with palivizumab on these patients and their economic management. METHODS: We identified those infants deemed to be at high risk, matching the population recently studied by the Cardiac Synagis Group, from the database of the cardiology department of the hospital. The number of patients under the care of the paediatric cardiologists admitted to Alder Hey Hospital with respiratory syncytial viral bronchiolitis over the last three seasons was identified from hospital coding records, and the database of the cardiology department. RESULTS: There are 131 patients at high risk each year. Of these, over the last three "bronchiolitis seasons", 39 infants have been admitted to the hospital with bronchiolitis due to the respiratory syncytial virus. This represents a hospitalisation rate of 10 per cent, as was seen in the study of the Cardiac Synagis Group. Using a monthly dose of 15 milligrams per kilogram for five doses, the cost per patient is 2,650 pounds sterling for the season. To treat the 131 patients seen at Alder Hey, therefore, would cost 346,800 pounds each year. Applying the reductions in hospitalisation identified in the study by the Cardiac Synagis Group to our population would produce an expected reduction in patients hospitalised from 13 to 7 per year, reducing the total length of stay in our hospital wards from 169 to 76 days, and in the paediatric intensive care unit from 93 to 21 days. This amounts to a potential saving of 190,800 pounds per year. Reducing transfers to more distant paediatric intensive care units for referrals refused because of lack of beds could save an additional 50,000 pounds. DISCUSSION: We estimate the net cost of introducing palivizumab for this population to be 106,000 pounds per year. There would, of course, be additional costs involved in setting up this service, as well as additional savings and benefits. This cost is comparable with other new biologic therapies now routinely used in the United Kingdom, such as etanercept for juvenile arthritis. There are, currently, no other obvious therapies that have the potential to reduce admissions to hospital and intensive care during the winter months, when beds are at their most scarce.

Antibodies, Monoclonal↗

Oral versus nebulized albuterol in the management of bronchiolitis in Egypt.

The efficacy of albuterol in the management of infants with first-time wheezing is controversial. This double-blind, placebo-controlled trial involved 128 Egyptian infants with first-time wheezing (mean age 5.9 months) who were randomly separated into four equivalent therapy groups: nebulized albuterol, nebulized saline solution, orally administered albuterol, and orally administered placebo. The nebulized therapy groups received two treatments 30 minutes apart; the oral therapy groups received one treatment. In addition, 41 infants with recurrent wheezing comprised an open-label control group who received two albuterol nebulizations. Chest radiographs, leukocyte counts, blood culture specimens, and nasal aspirate for viral antigen detection were obtained to confirm the clinical diagnosis of viral bronchiolitis. Respiratory and heart rates, clinical score, and oxygen saturation were recorded at baseline and 30 and 60 minutes after treatment. There was no difference among the four randomized groups in any of the outcomes except for an increase in heart rate of 10 beats/min in the nebulized albuterol group compared with a decrease in heart rate of 8 beats/min in the oral placebo group. No differences in the need for additional treatment were observed. Nebulized albuterol significantly improved the clinical score and reduced the respiratory rate of those with recurrent wheezing relative to those in the randomized groups. We conclude that nebulized albuterol is effective in the treatment of infants with recurrent wheezing, but there was no demonstrable efficacy of orally administered or nebulized albuterol in relieving the respiratory distress of infants with bronchiolitis in Egypt.

Administration, Oral↗

Acute and chronic airway responses to viral infection: implications for asthma and chronic obstructive pulmonary disease.

Despite the high clinical impact of established and emerging respiratory viruses, some critical aspects of the host response to these pathogens still need to be defined. In that context, we aimed at two major issues: first, what are the innate immune mechanisms that control common respiratory viral infections; and second, whether these mechanisms also cause long-term airway disease. Using a mouse model of viral bronchiolitis, we found that antiviral defense depends at least in part on a network of mucosal epithelial cells and macrophages specially programmed for immune-response gene expression. When this network is compromised, the host is highly susceptible to infection, but network components can be engineered to provide increased resistance to infection. Similar alterations appear in asthma and chronic bronchitis/chronic obstructive pulmonary disease, suggesting that evolving attempts to improve antiviral defense may also lead to inflammatory airway disease. Indeed, in genetically susceptible mice, respiratory paramyxoviruses cause a "hit and run" phenomenon that is manifested by the development of a permanent airway disease phenotype long after the infection has cleared. The phenotype can be segregated into individual traits to achieve more precise definition of just how viruses reprogram host behavior. Identifying specific components of the mucosal immune system that manifest an aberrant antiviral response may thereby allow for adjusting this response to improve acute and chronic outcomes after viral infection.

Animals↗

A comparison in chimpanzees of the immunogenicity and efficacy of live attenuated respiratory syncytial virus (RSV) temperature-sensitive mutant vaccines and vaccinia virus recombinants that express the surface glycoproteins of RSV.

Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis and pneumonia in children. The present study compares the level of attenuation, genetic stability and efficacy of three conditional-lethal temperature-sensitive (ts) mutants of the RSV A2 wild-type virus, designated ts-1, ts-1-NG1, and ts-4, in seronegative chimpanzees and also compares their efficacy with that of vaccinia virus recombinants that express the surface glycoproteins of RSV. Each of the ts mutants was highly attenuated in the lower respiratory tract, but still retained the capacity to induce significant rhinorrhoea. Each of the three ts mutants underwent partial reversion to a non-ts (ts+) phenotype during replication in a minority of the chimpanzees. The ts+ virus present in the upper respiratory tract of the chimpanzees did not spread to the lower respiratory tract and represented only a minority fraction of the virus present in the nasopharyngeal swab specimens. The ts mutants were highly immunogenic and provided resistance that effectively restricted RSV replication following virus challenge. In contrast, the vaccinia-RSV recombinants were less immunogenic. They protected the lungs of two of four chimpanzees challenged with RSV, but failed to protect the upper respiratory tract. The chimpanzee can serve as a model for the rapid evaluation of further attenuated live RSV vaccines.

Animals↗

Inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopathology.

TNF antagonists are effective treatments for rheumatoid arthritis and Crohn's disease, and have been tried with variable success in other diseases caused by immune damage. To test the hypothesis that viral lung diseases caused by respiratory syncytial virus or influenza virus are partly due to overproduction of TNF, we used anti-TNF antibody to treat mice with lung disease caused by these viruses. TNF depletion reduced pulmonary recruitment of inflammatory cells, cytokine production by T cells and the severity of illness without preventing virus clearance. These broad beneficial effects suggest that TNF antagonists might be tested as treatments of human viral lung diseases.

Animals↗

Clinical, physiologic, and roentgenographic changes after pneumonectomy in a boy with Macleod/Swyer-James syndrome and bronchiectasis.

Macleod/Swyer-James syndrome is an uncommon and complex disease characterized by roentgenographic hyperlucency of one lung or lobe due to loss of the pulmonary vascular structure and to alveolar overdistension. This syndrome seems to be an acquired disease that follows viral bronchiolitis and pneumonitis in childhood. It must be differentiated from many other causes of unilateral lung "transradiancy" on the chest roentgenogram, such as those related to congenital bronchial and/or vascular abnormalities. We here describe an 11-year-old patient with Macleod/Swyer-James syndrome and bronchiectasis resulting in severe recurrent bronchopulmonary infections. Despite the severe impairment of pulmonary function, the patient underwent resection of the right lung with progressive improvement of clinical and physiologic parameters.

Bronchiectasis↗

Effect of the thermodynamics of an infant plethysmograph on the measurement of thoracic gas volume.

Adult plethysmographs have frequency responses that are essentially flat over the range of frequencies encountered in the measurement of thoracic gas volume (TGV). An infant plethysmograph is necessarily much smaller than an adult model. This means that there is a smaller mean distance over which heat diffusion must occur between the air in the plethysmograph and its walls. This in turn leads to a much reduced thermal time constant. We examined the effects of thermal time constant of a 60 L infant plethysmograph on measurements of TGV in infants. The thermal time constant was measured by rapidly injecting 20 mL of air into the plethysmograph, and found to be 0.16 +/- 0.09s when the box was empty. We calculated from this time constant that measurements of TGV should be quite dependent on the frequency at which the associated panting maneuvers are performed. TGV was measured in 5 infants less than 6 months old in the recovery phase following acute viral bronchiolitis. When we performed a digital correction of the measurements, to compensate for the thermal time constant of the plethysmograph, the TGV values decreased by a mean of 12%. Agitating the air in the plethysmograph with a fan decreased the thermal time constant of the box and reduced measured TGV by a mean of 8.4%. These results indicate that thermodynamics of infant plethysmographs can be an important source of error in TGV measurements.

Algorithms↗

Right pulmonary agenesis associated with remaining bronchus stenosis, an equivalent of postpneumonectomy syndrome. Treatment by insertion of tissue expander in the thoracic cavity.

We report a case of right pulmonary agenesis with worsening of mediastinal shift during a viral bronchiolitis at the age of 5 months. The respiratory failure was due to stretching and narrowing of the remaining bronchus, as in postpneumonectomy syndrome. Weaning of respiratory assistance was possible after inserting a tissue expander in the empty side of the thoracic cavity. The correction of the shift brought a liberation of the left main stem bronchus. The main risk is heart compression. The child is now 3 years old and is at home. Filling of the prosthesis is done according to the clinical evolution.

Bronchial Diseases↗

[Rib fractures after chest physiotherapy: a report of 2 cases].

The 2000 French consensus conference for acute viral bronchiolitis management underlined the fundamental role of chest physiotherapy. According to Chalumeau and al., rib fractures were found out in 1/1000 children hospitalized for bronchiolitis or pneumonia. However, such complication of chest physiotherapy is exceptional. We report 2 cases with third to sixth lateral rib fractures after chest physiotherapy in infants with bronchiolitis. Despite the rarity of these complications, clinicians must keep in mind this etiology while facing rib fractures in infants.

Acute Disease↗

Pathological studies on camelpox lesions of the respiratory system in the United Arab Emirates (UAE).

Three dromedary camels (Camelus dromedarius), which died from generalized camelpox with lesions in the respiratory system, were investigated. Histopathological lesions in the lung consisted of small, sometimes confluent foci of proliferated bronchial epithelium, necrosis and fibrosis. Orthopoxvirus cameli was demonstrated in all three cases by transmission electron microscopy and the virus was isolated from the lung and trachea on Dubca cells. It was proved by restriction enzyme analysis of the viral DNA that the isolates were identical. Immunohistochemical examination showed numerous poxvirus antigen-positive cells in the bronchial epithelia. Immunolabelled material was found in bronchial epithelial cells with hydropic degeneration and in infiltrating macrophages.

Animals↗

Living-donor lobar lung transplantation experience: intermediate results.

OBJECTIVE: Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. METHODS: Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. RESULTS: There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). CONCLUSIONS: We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option.

Adolescent↗

The immunologic response to infection with respiratory syncytial virus in infants.

Fifty infants younger than six months, hospitalized for infection with respiratory syncytial virus (RSV), were studied by examination of serial samples of nasal secretion. Secretory neutralizing activity was measured by plaque reduction and secretory antibody by indirect fluorescence using conjugated antiserum to human IgA, IgG, or IgM. Secretory neutralizing activity during infection rose or fell fourfold with approximately equal frequency (20% and 26%, respectively). In contrast, levels of IgA antibody to RSV in secretions rose fourfold in 56%--65% of the infants and fell in none. The frequency of such rises in titer of antibody was directly related to age. In individual secretions the correlation between neutralizing activity and IgA antibody to RSV was poor: neutralizing activity was often found in the absence of detectable antibody, and IgA antibody to RSV was often nonneutralizing. Nevertheless, the development of IgA antibody to RSV correlated in time with the disappearance of virus from the respiratory tract. The timing of this secretory response is consistent with the hypothesis that antibody contributes significantly to cure of infection.

Antibodies, Viral↗