Biomedical subjects
Publications and source records attributed to J Riedler.
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The present study was undertaken to assess the practical and theoretical knowledge of paediatricians in regard of inhalation devices for the treatment of childhood asthma. Forty-one paediatricians (39 from different parts of Austria and 2 from Switzerland), all of them running hospital-based chest clinics, were tested in regard of 4 items (Diskhaler, Metered dose inhaler (MDI) with Aerochamber, cleaning of an Aerochamber and a Pari Junior jet nebuliser). Practical performance and theoretical knowledge were assessed. Scoring was done by one consultant using a score of 1-5, with 1 point being given for the poorest performance and 5 points for the best. Overall performance was acceptable with a median of 13 points (the maximum achievable score was 20), but there were some deficits in the practical use of special devices. Better training on the use of different devices for inhalation therapy of asthmatic children is desirable.
Viral colds are an important cause of respiratory symptoms in normal children. Studies in adults suggest that inflammation in the lower respiratory tract is associated with viral colds, but there are no data regarding inflammation and viral infection in the lower airway of normal children with colds. We, therefore, studied the lower airway of two groups of children: Group I, those with active coryzal symptoms and a respiratory virus isolated from bronchoalveolar lavage fluid (BALF); and Group II: asymptomatic children who had had a clinical cold within the previous 2 weeks and no respiratory virus in BALF. Both groups were compared to age- and weight-matched normal noninfected controls, who had had no coryzal symptoms for at least 8 weeks. Viruses isolated from BALF of Group I (n = 7) were: respiratory syncytial virus (n = 2), rhinovirus (n = 3), parainfluenza I (n = 1), and echovirus 11 (n = 1). Compared to normal controls, Group I had an increased BALF lymphocyte and neutrophil differential count (P < 0.05), a concomitant depressed alveolar macrophage differential count (P < 0.05), and increased BALF concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) (P < 0.05, n = 6), total protein (P < 0.05, n = 6) and albumin (P < 0.05, n = 7). Similar changes were seen in Group II (n = 22), with an increased BALF neutrophil (P < 0.05) and lymphocyte (P < 0.01) differential count, and increased concentrations of sICAM-1 (P < 0.01, n = 15), total protein (P < 0.0001, n = 9) and albumin (P = 0.05, n = 17). Our results suggest that inflammation and viral infection in the lower airway are present during active colds, and that inflammation is also present during the convalescent period.
This study sought to test the hypothesis that normal children exposed to parental cigarette smoke have increased bronchoalveolar lavage (BAL) fluid levels of soluble intercellular adhesion molecule (sICAM)-1. Cells and solutes from the lower airway of normal children were obtained by nonbronchoscopic BAL using three aliquots of 1 mL x kg body weight(-1) normal saline, prior to elective orthopaedic surgery. Children with evidence of recent or ongoing infection, atopic disease, previous history of wheeze, and chronic respiratory symptoms were excluded. Twelve children with parents who smoked (group 1) were paired with 12 age- and weight-matched controls with self-reported nonsmoking parents (group 2). There was no significant difference (group 1 versus 2) in the volume of BAL fluid recovered (median 29.0 versus 28.7 mL), the percentage of alveolar macrophages (92.5 versus 91.8%), neutrophils (1.1 versus 2.1%), lymphocytes (5.3 versus 5.6%) and eosinophils (0 versus 0%), and the total BAL fluid leukocyte concentration (80 versus 61 x 10(3) cells x mL(-1)). BAL fluid albumin concentration was similar between the two groups (0.033 versus 0.020 mg x mL(-1)). sICAM-1 was detected in all BAL fluid samples, and was significantly increased in group 1 (39.2 versus 22.5 ng x mL(-1), p<0.01). It was concluded that exposure of children to parental cigarette smoke is associated with increased soluble intercellular adhesion molecule-1 concentrations in the bronchoalveolar lavage fluid and this may reflect an altered activation of pulmonary immune cells.
Hypertonic saline challenge has become a standardized method for measuring airway responsiveness. However, there is still uncertainty about the occurrence of a late asthmatic response. Therefore, the present study was designed to assess a possible late asthmatic response after hypertonic saline challenge in children. Twenty-one children with mild to moderate bronchial hyperresponsiveness were studied. On days 1 and 2, forced expiratory volume in one second (FEV1) was measured hourly from 10:00 h to 22:00 h to assess diurnal variation of lung function. On the third study day, a hypertonic saline challenge was performed and FEV1 was measured as on control days. The possibility of a late asthmatic response was tested by comparing FEV1 levels up to 12 h after the challenge on the intervention day to FEV1 levels on control days. In no subjects were the FEV1 values following the challenge found to be considerably below the individual mean of the control days. Furthermore, a nonparametric approach was applied for each child and the population looked into as a whole. Again, no late asthmatic response was detectable. The results of this study suggest that in children with mild to moderate bronchial hyperresponsiveness a late asthmatic response does not occur 4-12 h after a 4.5% saline challenge.
Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (<2 yrs), group 2 (> or =2-< or =5 yrs) and group 3 (> or =6-< or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: <2 yrs and > or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children <2 yrs expressed less human leukocyte antigen (HLA)-DR (versus > or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children <2 yrs and > or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.
As part of the International Study of Asthma and Allergies in Childhood (ISAAC), the aim of our study was to determine the prevalence and severity of asthma, allergic rhinitis and eczema in Austrian schoolchildren, using an international standardised protocol. A questionnaire concerning symptoms and prior diagnosis of asthma, allergic rhinitis and eczema was completed by the parents of 3581 children aged 6-8 years. 3357 adolescents aged 12-15 years completed a written and video questionnaire at school. We also measured airway responsiveness to 4.5% saline in 519 adolescents selected from 8 randomly chosen schools. The prevalence of "wheezing in the last 12 months" was 9.9% (6-8 yrs) and 11.9% (12-15 yrs), the prevalence of "ever having had a diagnosis of asthma" was 4.4% and 6.3% in the above mentioned age groups. While 80% of the pupils had mild asthma (defined as less than 4 attacks of wheezing in the last year), 13% had moderate (4-12 attacks) and 7% had severe asthma (> 12 attacks). The 12-month prevalence of symptoms of allergic rhinitis was 13.4% (6-8 yrs) and 22.5% (12-15 yrs), a diagnosis of "hayfever at any time" was reported in 8.9% and 20.4%. The prevalence of a chronic rash in the past year was 6.9% (6-8 yrs) and 6.7% (12-15 yrs), while 10.4% and 5%, respectively, had had a diagnosis of "eczema at any time". Among 12- to 15-year-old adolescents in the entire study population (n = 3371), the calculated prevalence of bronchial hyperresponsiveness was 13.7%. The prevalence of asthma symptoms, rhinitis and eczema in Austrian schoolchildren is higher than that estimated so far and similar to other European countries except the UK. Further, the results show that the 12-month prevalence of asthma symptoms is twice as high as the lifetime prevalence of a diagnosis of asthma, suggesting that the condition is frequently underdiagnosed.
The results of a recent epidemiological study in Salzburg (Austria) showed that the prevalence of bronchial hyperresponsiveness (BHR) to hypertonic saline (HS) was 13.7% in schoolchildren aged 12-15 years. In the same study the prevalence of wheezing in the last 12 months was 11.9% and asthma had been diagnosed in 6.3%. To audit the relevance of these results and to offer medical treatment to children with newly diagnosed asthma, we invited all children who had had a positive bronchial provocation test (n = 99) or an abnormal lung function (defined as an FEV1 < 80% of the predicted value; n = 33) for clinical investigation. Seventy-five out of 99 children with BHR and 27/33 with an FEV1 < 80% of the predicted value attended the Respiratory Laboratory and a paediatric pulmonologist assessed the diagnosis on the basis of respiratory symptoms, physical examination and lung function test. In 26/53 children with asthma, the diagnosis was unknown. Although most children had mild asthma and normal lung function, half of these children had reduced physical activity. In 27/53 children with asthma, the diagnosis had already been known but, according to the specialist, had not been adequately treated. In 21/27 children with an FEV1 < 80% of the predicted value, this finding was clinically not relevant. The audit of the epidemiological study supported the assumption that asthma might be underdiagnosed and undertreated in our population.
The prevalence of asthma in school children has been reported to have increased, with wide variations between countries. To allow comparison of prevalence data, objective markers of asthma should be measured. Therefore, we assessed the prevalence of bronchial hyperresponsiveness (BHR) to hypertonic saline and its relation to asthma and allergy symptoms in 507 Austrian school children, aged 12-15 yrs in a cross-sectional, community based survey. These children were selected from 3,371 children who had answered a self-administered written questionnaire on asthma, hay fever, eczema and environmental factors. The prevalence of BHR to hypertonic saline was 14% and the majority (70%) of the children had mild BHR. The prevalence of wheeze in the last 12 months was 12% and of a diagnostic label of asthma was 6%. Fifty three per cent of the children with symptoms in the last 12 months and a diagnostic label of asthma had BHR, and 33% of those with symptoms in the last 12 months regardless of a diagnostic label of asthma showed a positive response to hypertonic saline. Atopic dermatitis, a diagnostic label of asthma, night cough apart from colds, wheeze in the past 12 months (but not "former wheeze") and male gender were significantly associated with increased response to 4.5% saline in the final logistic regression model. These results show that the prevalence of asthma symptoms in the last 12 months and the prevalence of bronchial hyperresponsiveness to hypertonic saline are twice that of a diagnosis of asthma and that asthma might be underdiagnosed in the present population. The response to hypertonic saline is most strongly associated with current asthma and allergy symptoms. A combination of a "diagnostic label of asthma" and "asthma symptoms in the last 12 months" might best reflect "current asthma" in epidemiological studies in this population.
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Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.
OBJECTIVE: To determine whether inhalation of hypertonic saline (HS) increases sputum expectoration in patients with cystic fibrosis (CF). METHODOLOGY: Ten adolescents with CF, who were receiving inpatient treatment for a pulmonary exacerbation, were enrolled in a controlled cross-over clinical trial. After inhalation of beta adrenergic drug to prevent possible broncho-constriction, each patient inhaled for 10 min either 0.9% isotonic saline (IS) or 6% HS prior to routine physiotherapy. The following day the patient received the alternative solution. Seven patients undertook a second block after 1-5 days. Outcome measures included weight of sputum, a visual analogue score to assess the subjective feeling of a cleared chest after physiotherapy, and spirometry. RESULTS: Sputum expectoration (median; Q1,Q3) from the beginning of the inhalation of HS or IS to the final spirometry measure 60 min post-physiotherapy was significantly greater after HS than IS [17.2g (11.7, 34.8) vs 11.3g (6.5, 16.1): P = 0.006]. A clinical score of the patient's own judgement of a cleared chest was significantly better after HS than IS. Spirometry results did not change following either of the two inhalations. CONCLUSIONS: These data show that the inhalation of 6% HS prior to physiotherapy can increase sputum expectoration in patients with CF and suggest that HS might be an effective, safe and cheap adjunct to regular physiotherapy in patients with CF.
There is still controversy about the most suitable method to measure bronchial hyperresponsiveness in children. In epidemiological surveys, nonisotonic aerosols are being used increasingly for bronchial provocation testing. Our aim was to study the acceptability, safety and correlation between two published bronchial challenge tests. Two standardized protocols--the inhalation of hypertonic saline (HS) and ultrasonically-nebulized distilled water (UNDW)--were performed in 36 children: 19 patients with the clinical diagnosis of mild-to-moderate asthma (7-12 yrs of age), and 17 control subjects (8-18 yrs of age). HS challenge involved stepwise inhalation of 4.5% saline (for 0.5, 1, 2, 4 and 8 min), whereas challenge with UNDW was performed as a single step protocol with 10 min inhalation of cold UNDW. Asthma medication was withheld prior to challenge testing. Thirty five subjects completed both challenge tests (one asthmatic patient did not return after UNDW challenge) in random order within a 7 day time interval. For HS a > or = 15% reduction in forced expiratory volume in one second (FEV1) from baseline was considered a positive response, and for UNDW a > or = 10% decrease. In 13 of the 19 asthmatic patients, but in none of the controls, a positive response was observed for UNDW. Fifteen out of 18 patients and one control subject had a positive response to HS. Twelve out of 18 asthmatic children responded to both challenges, three responded only to HS and three had no response to either challenge. There was a negative correlation between log provocative dose causing a 15% reduction in FEV1 (PD15) after HS and the maximum fall in FEV1 after UNDW (rs = -0.63; p < 0.005). The HS challenge had a lower acceptability than challenge with UNDW due to the unpleasant salty taste of HS. However, this did not inhibit the completion of the tests in any subject. The results of this study suggest a good correlation between response to hypertonic saline and ultrasonically-nebulized distilled water in children with mild-to-moderate asthma. A multiple step protocol might be safer when applied in field studies involving children.
Immunoglobulin A (IgA) plays an essential role in the local defence mechanism and is part of the immunologic system. It is transported to the endothelial surface either as a monomer or as a dimer of two molecules of IgA connected by a j-chain and attached to a secretory component. The aim of the present study was to assess the relation of salivary IgA to the age of children and to assess a possible influence by acute and chronic respiratory diseases. IgA was measured in the saliva of altogether 230 children by means of radial immunodiffusion (LC-IgA Partigen, Behring) following a standardised protocol. Relation to age was measured in 159 healthy children aged one month to 15 years. The median of IgA was 36 mg/l with a range of 3.5-291 mg/l. There was no statistically significant relationship between salivary IgA and the age of the children. Median IgA in the saliva of children without any respiratory disorders (n = 169) was 36 mg/l (3.5-291 mg/l), of children with acute respiratory diseases (n = 33) 51 mg/l (3.5-257 mg/l) and of children with chronic respiratory diseases (n = 28) 47 mg/l (3.5-165 mg/l). There was no statistically significant difference between these three groups. In conclusion, the results of this study show that IgA in the saliva of children may not be related to age or influenced by acute or chronic respiratory diseases.
The role of bronchoalveolar lavage (BAL) in children remains to be defined, and to date there has been no standardization of acquisition and processing of the BAL fluid. The aim of the present study was to evaluate a standardized protocol for obtaining, processing, and analyzing BAL fluid and to establish reference values for healthy children. Eighteen children 3 mo to 10 yr of age were lavaged with three 1-ml/kg aliquots of normal saline, using a flexible bronchoscope into the right middle lobe. The first aliquot was processed separately; the second and the third were pooled. There was a higher percentage of neutrophils and epithelial cells in the first aliquot. The number of total cells per milliliter (median, Q1 to Q3) in the first aliquot was 60 (45 to 90) x 10(3)/ml; in the pooled sample it was 155 (75 to 257) x 10(3)/ml. Percentages (median, Q1 to Q3) of different cell types in the pooled sample were: macrophages, 91% (84 to 94); lymphocytes, 7.5% (4.7 to 12.8); neutrophils, 1.7% (0.6 to 3.5); eosinophils, 0.15% (0.0 to 0.3). The ratio of helper/cytotoxic T-cells was 0.58 (0.4 to 1). The results of this study demonstrate that BAL, using a standardized protocol adjusting instilled fluid volume by weight, appears to be appropriate in children and that cellular and protein values from healthy children are, apart from differences in lymphocyte subsets, similar to those found in healthy adults.
The aim of the present study was to evaluate the clinical role of bronchoscopic and nonbronchoscopic bronchoalveolar lavage (BAL) in the diagnosis of infectious and interstitial lung disease in children. BAL was performed using three 1 mL.kg-1 aliquots of normal saline, with the flexible bronchoscope (Olympus 3.6 or 4.8 mm) wedged in a segmental or subsegmental bronchus of the lobe that showed most abnormality on chest radiograph. In seven children with severe diffuse lung disease who were intubated, a nonbronchoscopic suction catheter lavage was performed. Fluid cultures and cellularity were evaluated using identical methods for both techniques. Between January 1993 and April 1994, 41 BAL were performed in 32 children aged 2 months to 17 yrs (median 8 yrs). Of these lavages, 14 were in heart and heart-lung transplant recipients, 11 in children known to be immunocompromised, and 16 in children who had a lung biopsy for interstitial lung disease or who had presumed infective lung disease. Transbronchial biopsies (TBB) or open lung biopsies were performed coincident with 19 BAL procedures. In all transplant recipients without clinical symptoms, BAL and TBB cultures were negative and BAL cellularity was normal. TBB did not reveal infection or rejection in any of these patients. A diagnosis of infection was made by BAL in 1 out of 8 transplant recipients with clinical symptoms, and a diagnosis of rejection was made by TBB in 3 out of 8 patients. In 6 out of 11 BAL in immunocompromised children, an infectious agent was found in the BAL fluid. In three other patients who had an open lung biopsy, an interstitial lung disease was diagnosed. In these patients, BAL was abnormal but not diagnostic. In summary, BAL proved helpful in the diagnosis of infective lung disease, but had little value in the diagnosis of rejection or parenchymal noninfective lung disease in children.
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Non-isotonic aerosols are being used more commonly to perform bronchial provocation tests. In contrast to histamine and methacholine challenge tests they appear to have higher specificity and a higher predictive value. The aim of the present study was to assess the reproducibility of the response to challenge with 4.5% hypertonic saline administered via an ultrasonic nebulizer in children with mild to severe asthma. Seventeen children with asthma aged 10 to 14 years completed two or three challenge tests at the same time of day within a 10 day period. Of these 17 children 9 had mild, 4 moderate, and 4 severe asthma. Children inhaled 4.5% hypertonic NaCl from an ultrasonic nebulizer with an output of 1.9 to 2.5 mL/min (Timeter) using the protocol developed by Anderson with modifications. A fall in forced expiratory volume in 1 second (FEV1) from baseline of 15% or more was considered a positive response and PD15 was calculated. In 16/17 subjects a greater than 15% fall in FEV1 occurred consistently on all study days. One subject with moderate asthma had a less than 15% fall in FEV1 on both study days. The coefficient of repeatability for PD15 was 1.8. This equals 0.85 of a doubling dose difference between the two or three measurements of PD15. The cumulative time of aerosol inhalation causing a fall in FEV1 > or = 15%) (PT15) showed a coefficient of repeatability of 1.59, similar to 0.67 doubling dose difference. The PD15 and PT15 were highly significantly correlated. The 4.5% NaCl challenge test yields good reproducibility in children with mild to severe asthma under laboratory conditions.