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Biomedical subjects

F Midulla

Publications and source records attributed to F Midulla.

24 records · Page 2Linked to original sources

Productive infection of isolated human alveolar macrophages by respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in children and individuals with cell-mediated immunodeficiencies. Airway epithelial cells may be infected with RSV, but it is unknown whether other cells within the lung permit viral replication. We studied whether human alveolar macrophages supported RSV replication in vitro. Alveolar macrophages exposed to RSV demonstrated expression of RSV fusion gene, which increased in a time-dependent manner and correlated with RSV protein expression. RSV-exposed alveolar macrophages produced and released infectious virus into supernatants for at least 25 d after infection. Viral production per alveolar macrophage declined from 0.053 plaque-forming units (pfu)/cell at 24 h after infection to 0.003 pfu/cell by 10 d after infection and then gradually increased. The capability of alveolar macrophages to support prolonged RSV replication may have a role in the pulmonary response to RSV infection.

Blotting, Northern↗

Respiratory syncytial virus infection of human cord and adult blood monocytes and alveolar macrophages.

We studied the permissiveness of human leukocytes, blood monocytes, alveolar macrophages, and cord blood monocytes to infection with respiratory syncytial virus (RSV). Specific immunofluorescence was used to determine the percentage of infected leukocytes. The results indicated that monocytes were the most susceptible human leukocyte to in vitro infection with RSV. Polymorphonuclear leukocytes demonstrated no specific fluorescent staining after 24 h of exposure to RSV, whereas peripheral blood nonadherent mononuclear cells demonstrated a low percentage of positive cells, with a mean of 6 +/- 1% SE. In contrast, 37 +/- 5% of monocytes expressed RSV antigen after viral exposure. Exposure of monocytes to lipopolysaccharide (LPS) for 1 h prior to RSV increased the percentage of infected cells to 48 +/- 6% and stimulated their secretion of prostaglandin E2 (PGE2) and alpha tumor necrosis factor (TNF). Intrinsic mononuclear phagocytic factors influencing the permissiveness to RSV were studied by determining infection of adult and cord blood and alveolar mononuclear phagocytes (MP). Alveolar and blood MP simultaneously isolated from adult donors were similarly infected by RSV, which varied with the viral dose. Cord blood MP were more susceptible to RSV infection than were adult MP, 58 +/- 9% infected versus 37 +/- 5%, respectively (p less than 0.05). Treatment with LPS for 1 h prior to RSV exposure did not increase infection of cord blood MP as seen with adult blood MP. However, LPS can induce human monocytes to secrete cytokines with antiviral activity, and our results indicate that both gamma interferon and TNF, independently or in combination, prevented infection of monocytes in a dose-dependent manner.

Adult↗

Parental smoking enhances bronchial responsiveness in nine-year-old children.

We studied the relationship between parental smoking habits and atopy and bronchial responsiveness (BR) in 9-year-old, non-selected schoolchildren. A questionnaire on respiratory disease and maternal and paternal smoking habits was administered to one parent. Skin prick tests using the most common allergens present in central Italy, a flow-volume spirometric test, and a bronchial provocation test using carbachol in increasing doses were performed. Male children with smoking parents had significantly increased BR when compared to those whose parents did not smoke (Odds Ratio (OR) = 4.3, p = 0.009). No such significant increase in BR was found in female children of smoking parents (OR = 1.5, p = 0.4). The relationship between BR in children and smoking in parents was stronger in asthmatics (p = 0.02), but was still significant after controlling for asthma and atopy. Bronchial responsiveness was significantly correlated with atopy (p = 0.001). This was also true for nonasthmatic children and for both males and females separately. Male children of smoking parents had increased reactivity to allergens as assessed by the skin prick test index (p = 0.001). It is hypothesized that passive smoking, by increasing the frequency of BR and of atopy, may increase the risk of asthma in childhood and particularly in boys.

Adult↗

Controlled studies of childhood asthma self-management in Italy using the "open airways" and "living with asthma" programs: a preliminary report.

The concept of self-management for childhood asthma was introduced to Italy through a scientific exchange agreement with the United States. Two self-management programs, Living with Asthma (LWA) and Open Airways (OA), are being evaluated in three studies, two of which (Pilot and Atri-Viterbo) were conducted by the Respiratory Service of the Pediatric Department of the University "La Sapienza" in Rome and one by 14 Italian university pediatric respiratory centers (Project Italia). In October 1985, 20 children and their 40 parents were enrolled in the Pilot Study. One hundred percent of the mothers and children and 70% of the fathers attended all of the sessions. Theoretical knowledge about asthma and knowledge of asthma self-management behavior were assessed three times by a questionnaire: at the beginning of the program, at the end of the program and one year later. Significant improvements in knowledge of asthma and in knowledge of asthma self-management behavior were demonstrated by both parents and children at the end of the program and one year later. Analysis of clinical symptoms and drug consumption indicated a statistically nonsignificant trend towards a reduction of asthma severity in the year after the program. In the Atri-Viterbo study 8229 children were initially screened by a questionnaire. One hundred eighty-two children with asthma (2.4%) were identified and invited to participate in a self-management program. Open Airways was used in a shortened version. Only 29 families in Atri (22% of the eligible families) and 24 families in Viterbo (50%) ultimately agreed to participate in the program. A comparison of these families with those who did not participate showed that higher social status (p less than 0.001) and more severe asthma (p less than 0.05) were significantly associated with participation. Attendance by mothers and children was 78% in Atri and 61% in Viterbo. Only 5% of the fathers regularly attended the program. Parents who received the program registered a statistically significant increase in knowledge of asthma and knowledge of asthma self-management behavior relative to controls (+13% versus -4%; p less than 0.05). Fourteen university-based pediatric respiratory centers participated in Project Italia, in which the LWA and OA programs were compared in both full length and shortened versions (8 versus 4 h). Four hundred children and their families were enrolled in the study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Cytokines in the nasal washes of children with respiratory syncytial virus bronchiolitis.

Although respiratory syncytial (RS) virus is the major cause of bronchiolitis and pneumonia in young children, the factors that regulate the associated lung inflammation have not been defined. The levels of interleukin (IL)10, IL-12, and interferon (IFN) were determined in the nasal wash samples from 20 infants with a clinical diagnosis of bronchiolitis, seven with confirmed RS virus infections and 9 control children without respiratory illnesses. IL-10 levels were significantly higher in acute nasal wash samples (1-4 d post hospitalization) from RS virus-infected infants than in convalescent samples from these children (14-21 d post-hospitalization), from children with other forms of bronchiolitis and from control children. In contrast, only one RS virus-infected infant had detectable IL-12 in an acute nasal wash sample. IFN activity was not detected in any samples from RS virus-infected children. RS virus infection stimulates IL-10 expression but not IL-12 and IFN, possibly contributing to an ineffective cell-mediated immune response.

Acute Disease↗