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Biomedical subjects

F Midulla

Publications and source records attributed to F Midulla.

At least 19 recordsLinked to original sources

Spondylodiscitis after bilateral sequential lung transplantation in a patient with cystic fibrosis.

We report the case of a 24-year-old woman with cystic fibrosis in whom spondylodiscitis developed after bilateral sequential transplantation. The diagnostic work-up included magnetic resonance imaging, computed tomography-guided disk biopsy, histological examination, and cultures of disk specimens. The infective organism was D group Streptococcus and the patient was successfully treated with intravenous piperacillin followed by oral ampicillin. To our knowledge, this is the first reported case of spondylodiscitis after lung transplantation.

Adult↗

3-min step test and treadmill exercise for evaluating exercise-induced asthma.

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3-min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9 +/- 0.9 yrs) underwent a 3-min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV1). After both exercise challenges all subjects did serial spirometry and the lowest FEV1 recorded over time was used to calculate the fall in FEV1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV1) and the area above the FEV1 curve (AAC0-30 min) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV1 was significantly higher for treadmill exercise than for the step test (15.0 +/- 7.5 versus 11.7 +/- 5.9); and the AAC0-30 min was larger for treadmill than for the step test (-261.6 +/- 139.9% versus -197.3 +/- 105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV1 and baseline lung function, or between % fall in FEV1 among groups defined by habitual physical activity. Although the 3-min step test yields a lower % fall in forced expiratory volume in one second (FEV1) and a lower value of the area above the FEV1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.

Adolescent↗

Flexible endoscopy of paediatric airways.

Paediatric fibreoptic bronchoscopy is used for ever wider indications, and increasingly used in many contexts, including paediatric and neonatal intensive care. The report of this Task Force contains an overview on the current applications of paediatric bronchoscopy. The report discusses the facilities and equipment needed for the procedure, including the newly developed bronchoscopes which are allowing intervention even in very small children. The indications of both flexible and rigid bronchoscopes in the context of newer and smaller flexible endoscopic equipment are also considered. The care of the instruments, including disinfection and sterilisation, is fully documented. Patient management is described, including the relative merits of conscious sedation and general anaesthesia, as well as special settings for the procedure, including the needs in intensive care. Special procedures, increasingly performed bronchoscopically are described. These include bronchoalveolar lavage, endobronchial and transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of bronchoscopic procedures, including bronchoscopic research in children. Advances in instrumentation, and also improved anaesthetic techniques, allow fibreoptic bronchoscopy to be safely performed in even very small, sick infants, provided proper precautions are taken.

Airway Obstruction↗

Cellular and noncellular components of bronchoalveolar lavage fluid in HIV-1-infected children with radiological evidence of interstitial lung damage.

Children with acquired immune deficiency syndrome (AIDS) commonly have recurrent infectious and noninfectious lung complications that ultimately end in death. To study the intensity of alveolar inflammation and to evaluate the clinical utility of bronchoalveolar lavage (BAL) in children with HIV-1 infections, we retrospectively analyzed differential cell counts, lymphocyte subsets, and fibronectin and hyaluronic acid concentrations in BAL fluid of 18 HIV-1-positive children (9 boys, mean age 3.5 years, range 5 months-8 years) with radiological evidence of interstitial lung disease, and 19 control children who had undergone BAL for clinical indications not involving the lung parenchyma (13 boys, mean age 3 years, range 2 months-14 years). BAL fluid from 89% of the HIV-1 infected children showed CD8+ve lymphocytic alveolitis expressing HLA-DR, CD54, and CD 69 antigens. BAL fluid from HIV-infected patients typically contained markedly increased percentages and numbers of lymphocytes (P < 0.0001) and eosinophils (P < 0.04) and significantly higher concentrations of albumin (P < 0.05) and fibronectin (P < 0.0006) than fluids from control children. Whereas BAL cellular components did not differ in P. carinii-positive and P. carinii-negative HIV-1-infected children, fibronectin concentrations were significantly higher in P. carinii-positive than negative children. BAL cell differentials and noncellular components were related neither to severity of disease nor to patients' disease progression. These findings indicate that BAL is useful in studying the intensity of lung inflammation in children with HIV-1 infections and radiologically documented interstitial lung disease, but provides no information on the subsequent clinical course.

Bronchoalveolar Lavage Fluid↗

Sleep apnoea in children with diabetes mellitus: effect of glycaemic control.

AIMS/HYPOTHESIS: Patients with diabetes mellitus commonly have cardiovascular autonomic dysfunction and an abnormal ventilatory pattern during sleep. Few data are available on these changes in childhood diabetes. We investigated whether young diabetic children with or without diabetic neuropathy have ventilatory dysfunction during sleep and if so, whether these autonomic changes are related to the duration of diabetes and glycaemic control. METHODS: We studied 25 children with insulin-dependent diabetes mellitus (19 boys, mean age 7.72 +/- 1.99 years). All patients were insulin-dependent at diagnosis; blood samples for HbA1c assay were collected on the morning before testing and at 3-month intervals during the preceding year. Patients and control subjects (20 age-matched healthy children, 15 boys) underwent overnight polysomnography. RESULTS: More diabetic patients than control subjects had sleep apnoeas (p = 0.006); apnoeas in patients also lasted longer (p = 0.07). Patients with poorly controlled diabetes had more apnoeas than patients with well-controlled diabetes and than healthy control subjects (p < 0.0001). Respiratory events during sleep correlated significantly with glycaemic control (r = 0.360; p = 0.09) and with the duration of diabetes (r = 0.430; p = 0.04). CONCLUSION/INTERPRETATION: We conclude that respiratory control is compromised very early in children with diabetes. These anomalies are closely related to the duration of diabetes and to glycaemic control. In young children with diabetes, screening of ventilatory control using recording techniques that are simpler than polysomnography could provide an early indication that an adverse cardiopulmonary reaction has begun.

Blood Glucose↗

Bronchoalveolar lavage in children with chronic diffuse parenchymal lung disease.

The aim of the present study was to compare cellular and noncellular components of bronchoalveolar lavage fluid (BAL) in a group of children with a diagnosis of chronic diffuse parenchymal lung disease (cDPLD) and a group of children without parenchymal lung disease undergoing BAL for various clinical indications (control group). We evaluated cellular and non-cellular components (total proteins, albumin, hyaluronic acid, and fibronectin) in BAL fluid from 14 children (7 boys and 7 girls; mean age 9.2 years, range 5 months to 18.4 years) fulfilling the clinical and radiological diagnosis of chronic cDPLD, and in 19 controls without evidence of lung disease. The 14 patients were assigned to two study groups: early-stage cDPLD (6 patients; age range 5 months to 5.2 years; duration of illness, 5-7 months) and long-standing cDPLD (8 patients; age range 9.6-18.4 years; duration of illness, 1.2-17.6 years). Ninety-three percent of the patients with cDPLD had at least two BAL constituents outside normal limits, with high numbers of cells, including all types of alveolar cells, but especially lymphocytes and foamy macrophages. These findings indicate a mixed, predominantly lymphocytic alveolitis. Our patients also had a significant increase in two noncellular BAL components, namely fibronectin and hyaluronic acid. BAL samples from children with long-standing cDPLD contained increased numbers of lymphocytes, whereas samples from children with early-stage cDPLD contained increased percentages and numbers of foamy macrophages and increased concentrations of fibronectin, hyaluronic acid, and albumin. In conclusion, we clearly identified an abnormal BAL profile in our group of cDPLD patients. Moreover, BAL findings differentiated younger cDPLD patients in the early stages of their illness from old patients with long-standing disease.

Adolescent↗

Bronchoalveolar lavage cell analysis in a child with chronic lipid pneumonia.

In an asymptomatic 4 yr old child with radiographic evidence of parenchymal lung disease, bronchoalveolar lavage (BAL) yielded the diagnosis of chronic lipid pneumonia caused by chronic aspiration of mineral oil given as a laxative. BAL analysis showed a marked reduction in the total number of alveolar macrophages; almost 70% of these cells contained intracytoplasmic lipid vacuoles. It also disclosed lymphocytic (cytotoxic/suppressor) alveolitis. A high percentage of lymphocytes expressed antigen markers of activation (human leucocyte antigen (HLA)-DR), CD54 and CD25). BAL analysis 18 months after mineral oil intake revealed that lymphocytes bearing antigen markers of activation had markedly decreased whereas alveolar macrophages (normal and lipid-laden) had increased. A subsequent whole lung BAL was considered unnecessarily invasive in this otherwise healthy child.

Bronchoalveolar Lavage Fluid↗

Validation of automated sleep analysis in normal children.

With the aim of determining normal reference values for our sleep laboratory and evaluating the reliability of automated analysis for scoring polysomnographic studies in children, we recorded polysomnograms in 16 healthy boarding-school children. Sleep recordings were obtained with a computer system (Medilog SAC, Oxford Instruments). Polysomnographic variables were monitored continuously on a 16-channel recorder equipped with a video. Data were acquired on optical disk for computer-assisted data interpretation. Sleep stages and respiratory events were also scored visually by operator. Comparison with visual scores showed that the computer system significantly overscored wakefulness (W) (p<0.02) and stage IV (p<0.001) and underscored stage II (p<0.001) and rapid eye movement (REM) sleep (p<0.001). It also assigned respiratory events a higher score than did visual scoring, as shown by the higher apnoea index (AI) and hypopnoea index (HI) (AI p<0.03; HI p<0.001). Regression analysis showed a significant correlation between visual and automated scores for central (r=0.679; p<0.004) and obstructive apnoea (r=0.631; p<0.008). Computer apnoea scores did not correlate with visual scores. Much remains to be done before computer-based scoring systems can be relied upon, without visual scoring, for polysomnographic sleep studies in children. Their main advantage at present is that they offer a convenient means of saving paper, space and time.

Apnea↗

Asthma self-management programmes in a population of Italian children: a multicentric study. Italian Study Group on Asthma Self-Management Programmes.

This study was designed to answer three main questions: 1) Does asthma self-management education reduce asthma morbidity? 2) Are the two programmes "Living With Asthma" and "Open Airways" equally effective in doing so? 3) Is a shortened version of these programmes (4 weeks) as effective as the longer original programme (8 weeks)? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma, who were stratified by disease severity, gender and age, and then randomly assigned to an Experimental group which received an educational programme or to a Comparison group, which did not. Of the 312 children selected, 209 (114 Experimental and 95 Comparison) completed the educational protocol and a 1 year follow-up. Data recorded during the last 2 months of follow-up, 10 months after the educational intervention, showed that the Experimental group required significantly fewer emergency treatments: this reduction was more evident in the more severe asthma cases. In the Experimental, but not in the Comparison group, patients with more severe asthma consumed more medications than patients with milder asthma "Open Airways" yielded, in some cases, better results than "Living with Asthma": but a type 2 error is possible. The standard and the shortened programmes proved equally effective. In conclusion, following education, regardless of receiving a short or long educational programme, asthma patients use emergency care services less and use medications more appropriately in comparison with standard care without education. This suggests that short educational programmes can be highly cost-effective in children with asthma.

Asthma↗

Bronchoalveolar lavage studies in children without parenchymal lung disease: cellular constituents and protein levels.

We evaluated bronchoalveolar lavage fluid (BAL) for cellular constituents, concentration of total protein (TP), albumin (AL), fibronectin (FN), and hyaluronic acid (HA) in 16 children aged 2-32 months without pulmonary inflammatory or parenchymal disease to establish reference values. We compared our data to those reported in older children and in normal adult volunteers. BAL results were obtained simultaneously from the right middle lobe and the lingula. Results indicated that children younger than 3 years of age had a higher number of cells/mL than older children and adults (59.9 x 10(4) vs. 17.6 x 10(4) and 12 x 10(4)). Differential cell count revealed that the percentages of alveolar macrophages (AM), lymphocytes (LYM), and eosinophils (EOS) were similar to those obtained in older children and in adults, whereas the percentage of neutrophils (NEU) was higher in younger children (NEU 5.5 vs 1.6 and 1.2%, respectively) than in older children and adults. The latter difference was even greater in infants under 12 months of age (NEU 7.6%). The concentrations of TP, AL, FN, and HA in children's BAL samples were compared to values reported for adults. There were no differences between infants and children 13-32 months of age or normal adults. BAL fluid obtained simultaneously from the middle lobe and lingula were not significantly different. In conclusion, this is the first report on BAL values (cellular and noncellular constituents) in children younger than 3 years. The results may be used as reference values for further studies in children with parenchymal lung disease in this age group.

Adult↗

Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages.

Thirteen previously healthy children with acute onset of severe lower respiratory tract signs and symptoms underwent bronchoscopy and bronchoalveolar lavage (BAL) for diagnostic purposes. BAL samples were assessed for viral, bacterial, mycobacterial, and fungal cultures. Cytospin preparations of BAL cells were assessed for expression of respiratory syncytial virus (RSV), HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children were assessed for viral replication. Three children had bacterial pneumonia and 6 were infected with RSV. BAL cells from RSV-infected children demonstrated viral protein expression. Alveolar macrophages were the predominant cell type recovered by BAL and demonstrated coexpression of RSV, HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children replicated RSV by infectious center assays. Thus, alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate the local immune response or lung injury due to this virus.

Bronchoalveolar Lavage Fluid↗

Early wheezing and breast feeding.

There is uncertainty as to whether breast feeding protects against subsequent illnesses; it has been suggested that breast feeding may have some protective effects on the severity of long-term outcome of bronchiolitis and in reducing morbidity. We have assessed the effects of breast feeding in 266 patients and 199 controls, all patients were early wheezers (i.e., under 2 years old). Between these groups we found differences in socioeconomic, environmental, and atopic conditions, but there were no significant differences in the numbers who had been breastfed. However, within the group who had had early wheezing we found that infants who had been breastfed for at least one month subsequently had less severe wheezing. These results suggest that breast feeding may be a protective factor for early wheezing only during the first month of life, and a delaying factor in the following months.

Breast Feeding↗

Enhanced allergic sensitisation related to parental smoking.

The objective of this study was to assess the role of parental smoking in changes, after a four year interval (1983-7), in the prevalence and severity of the atopic state in 166 pre-adolescent children. Allergy skin prick tests were related to parental smoking habits and their changes during this same interval. The total number of cigarettes smoked by parents decreased in 56 families while it increased in only 16. Boys had significantly more persistently positive skin tests and changed more frequently from negative to positive. The skin test index did not show significant changes in girls. This index did not change in children of persistent non-smokers or those starting to smoke during this period, while it increased among sons of those that quit smoking and of persistent smokers. This was not only due to those boys who became skin test positive during follow up. When analysis was restricted to 14 boys who had been skin test positive in 1983 and whose parents were persistent smokers, the index increased in eight, remained unchanged in four, and decreased in only two. This report supports the hypothesis that parental smoking is a factor that, together with specific allergenic exposure, may enhance allergic sensitisation in children.

Child↗

Bronchiolitis in the history of the asthmatic child.

In a retrospective analysis of the history of 1,700 asthmatic children, 167 (9.8%) were found to have had bronchiolitis during the first 2 years of life. These 167 cases with asthma and bronchiolitis were matched against 215 selected cases of asthma without bronchiolitis. Both groups attended our Ambulatory Care Unit for Asthma. Data were collected from the clinical cards of the children. Asthmatics who had bronchiolitis were found to have an earlier onset of asthma (p less than 0.001), earlier resolution of symptoms (p less than 0.05 total; p less than 0.01 females), and less evidence of atopy (p less than 0.005). It is suggested therefore that the bronchial hyperreactivity in asthma following bronchiolitis may have different underlying mechanisms than in the typical atopic case, without preceding bronchiolitis. Long-term follow-up studies in infants with bronchiolitis are still necessary in order to clarify the process by which bronchiolitis predisposes to bronchial hyperreactivity and asthma. The consequences of the viral infection itself may lead to pathophysiological processes that promote bronchial hyperreactivity. On the contrary, an underlying condition of bronchial hyperreactivity could be the "primum movens" of the bronchiolitis itself.

Asthma↗

Virus-induced alterations in macrophage production of tumor necrosis factor and prostaglandin E2.

The cellular immune response to respiratory syncytial virus (RSV) is felt to contribute to viral clearance and/or the inflammation accompanying pulmonary infections with this virus. Both tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) are important regulatory mediators of the cellular immune response. We examined the production of these mediators from purified human alveolar and blood mononuclear phagocytes (MP) after RSV infection in vitro and compared production induced by virus with that induced by lipopolysaccharide (LPS). RSV infection of alveolar MP did not alter PGE2 production but increased expression of TNF alpha mRNA paralleled by increased secretion of immunoreactive and biologically active TNF. TNF production by alveolar MP was dependent on the infectious dose of virus and occurred early in the viral replication cycle. In contrast, RSV had minimal effects on blood MP production of TNF and PGE2. However, blood MP (and not alveolar MP) infected with RSV and costimulated with LPS demonstrated a 1.7-fold increase in PGE2 levels compared with LPS alone (P less than 0.001). Therefore, RSV has differential effects on human alveolar and blood MP production of these immunoregulatory molecules.

Adult↗