Lower Respiratory Illness In Infants Research Articles

Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus

Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.

Effects of RSV infection on pulmonary surfactant protein SP-A in cultured human type II cells: contrasting consequences on SP-A mRNA and protein

Respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory illness in infants and children. Surfactant proteins A (SP-A) and D (SP-D) play critical roles in lung defense against RSV infections. Alterations in surfactant protein homeostasis in the lung may result from changes in production, metabolism, or uptake of the protein within the lung. We hypothesized that RSV infection of the type II cell, the primary source of surfactant protein, may alter surfactant protein gene expression. Human type II cells grown in primary culture possess lamellar bodies (a type II cell-specific organelle) and the ability to express surfactant protein mRNA. These cells were infected with RSV (by morphology and antibody binding). Surfactant protein mRNA levels determined by quantitative RT-PCR indicated a marked increase in SP-A mRNA levels (3-fold) 24 h after RSV exposure, whereas SP-D mRNA levels were unaffected. In contrast to mRNA levels, total SP-A protein levels (determined by Western blot analysis) were decreased 40% after RSV infection. The percentage of secreted SP-A was 43% of the total SP-A in the RSV-infected cells, whereas the percentage of secreted SP-A was 61% of the total SP-A in the uninfected cells. These changes in SP-A transcript levels and protein secretion in cultured human cells were recapitulated in RSV-infected mouse lung. Our findings suggest that type II cells are potentially important targets of RSV lower respiratory infection and that alterations in surfactant protein gene expression and SP-A protein homeostasis in the lung may arise via direct effects of RSV.

Maternal vaccines

Acute lower respiratory illness (LRI) is the leading cause of disease worldwide as measured by disability-adjusted life years. New strategies are necessary to decrease the disease burden that is largely borne by infants. Respiratory syncytial virus is the most important cause of LRI in infants. Lower respiratory illness can be prevented by endowing infants with high levels of neutralizing antibodies from mothers whose antibodies are boosted during pregnancy with a potent subunit vaccine. Another important cause of infant mortality is group B streptococcus sepsis in the neonatal period; maternal immunization with a group B conjugate vaccine could prevent this devastating infection.

Prevention of respiratory syncytial virus infections.

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Lower respiratory illness in infants and young children with cystic fibrosis

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized-agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V′max, FRC) were measured on admission, on Day 10 of hospitalization, and as outpatients 1–2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z-scores. Upon admission, flows were decreased, and FRC was increased in both groups; there were no differences between the groups. The change in pulmonary function from admission to Day 10 of hospitalization was not different for the two groups. From admission to outpatient follow-up after hospitalization, there was a significant increase in flows for the steroid group, but not for the placebo group. In addition, the direction of change in FRC was significantly different for the two groups; the steroid group had a small decrease in FRC, while the placebo group had a small increase in FRC. These findings suggest that the addition of intravenous hydrocortisone to the standard treatment of CF infants hospitalized for a LRI may produce a greater or a more sustained improvement in lung function following hospitalization. Pediatr. Pulmonol. 1997;24:48–51. © 1997 Wiley-Liss, Inc.

Lower respiratory illness in infants and low socioeconomic status.

Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed.

Environmentally Mediated Disorders of the Respiratory Tract

Although much of the evidence in environmental lung disease remains equivocal, some environmental exposures are known to be clinically relevant. Ambient air pollution remains of concern as a source of morbidity, particularly for susceptible populations such as persons with asthma, chronic obstructive pulmonary disease, or cardiac disease and the elderly. The adverse effects of several components of indoor air pollution have been established. Environmental tobacco smoke contributes to lower-respiratory illness in infants; office workers exposed to thermophilic actinomycetes contaminating ventilation systems have developed hypersensitivity pneumonitis; and in the home, components of house dust and fungus spores may provoke asthma via immediate hypersensitivity. The evidence is less compelling for a link between other exposures and disorders of the respiratory tract. For example, formaldehyde may be responsible for provoking vague respiratory symptoms and even nasal cancers; however, the associations are unproved. Likewise, the relation between low-level exposure to asbestos and the development of lung cancer, although a concern, is not conclusively established. The clinician should be aware of practical measures for patients who inquire about air cleaning. Often, relatively simple solutions are effective. A knowledge of sources and exposures as well as an understanding of the principles of inhalation lung injury should prove useful in directing patient care.