key: cord-0010140-vfj8lsxl
authors: Zach, Maximilian
title: Conference Report
date: 2005-12-12
journal: Pediatr Pulmonol
DOI: 10.1002/ppul.1950040208
sha: 379159ea697aeedd2664f94f477820c5f0a1ee51
doc_id: 10140
cord_uid: vfj8lsxl

nan

At the 1987 meeting of the European Pediatric Respiratory Society (EPRS), invited lectures and free papers presented a cross-sectional overview of European activities in one of the youngest subspecialties of pediatrics. The researchers-a multilingual group with widely differing professional, national, and cultural backgroundsconvened for presenting their work, exchanging ideas, educating each other, and, thereby, serving the common goals represented by the Society.

The following Abstracts of the free papers read at the meeting, while fairly accurately presenting current European research activities with lung diseases in children, also feature a certain lack of scientific homogeneity. This reflects the marked differences in the state of development of pediatric pulmonology in various countries and at their respective institutions. In an increasing number of teaching centers the subspecialty is gaining recognition and support, and is thus prospering; but the majority of European pediatric institutions still lack highly educated personnel as well as specialized diagnostic and therapeutic facilities. There are many reasons for this. Basic structural differences in health care services and educaeducational programs between various countries, together with factors related to more fundamental differences between the peoples of the continent, often hamper the exchange of ideas and dissemination of expertise, which would be the prerequisite for the development of uniform professional standards. Also, frequently voiced

misgivings about further subspecialization within pediatrics are, at times, aimed at pediatric pulmonology. However, by holding back progress in any subsegment of pediatrics, even some of the most influential leaders of the conservative pediatric establishment may, in fact, weaken what they intend to protect: the integrity of pediatrics itself. Last, but not least, pediatric pulmonology is struggling to establish itself in a period of wide-spread reductions in medical and academic budgets.

Yet, against all these odds, the new subspecialty is thriving in most of Europe, pioneered and supported by a modest number of dedicated, dynamic young researchers. To date, this lively crowd congregates in two societies: the EPRS and the more physiologically oriented Pediatric Group of the European Society for Clinical Respiratory Physiology (SEPCR). The two organizations have established close ties and share the leaders in the field among their membership. In addition, national societies and working groups have been established, providing momentum on the local scenes of different countries. The recent growth of all these organizations provides the pleasure of witnessing a steadily increasing expertise, improving academic standards, and dedicated research, that are gaining in both quantity and quality. The Helsinki meeting can rightfully be considered as a milestone in this ongoing development.

-MAXIMILIAN ZACH, MD 

Progress in our understanding o f pulmonary immunopathology will help to lower the risks of disease, to improve the treatment of infections and possibly to develop pharmacological means of stimulating compromised o r compensatory immune mechanisms. As a rule, selective defects of pulmonary immune mechanisms will lead to infection if additional defects develop or coexist, e. g. IgG-subclass deficiencies in addition to IgA deficiency. Combined humoral immunedeficlencies predispose to recurrent o r chronic infections with purulent bacteria. In congenital T-cell deficiency viral, fungal, protozoal and mycobacterial organisms prevail. Immunodeficiencies following HIV, EEV or other viruses result in clinical syndromes resembling congenital immunedeficiency. In contrast, immunesuppression causes a wide spectrum of immunedysfunction depending on the treatment regimen. Most respiratory infections in such patients result from aspiration o r hematogeneous spread of endogenous organisms. Reactivation o f Herpes Virus o r Cytomegalovirus and acquisition of Measles, Legionella and Pneumocystis carinii are important other causes of infection. In contrast, Mumps, Rubella, Hepatitis 6 , EBV and Parainfluenza Type I, Polio, Echo and Coxsackie Viruses appear o f little significance in these patients. Analysis of several series of pulmonary infections in immunosuppressed children has shown Pneumocystis to be the most frequent organism followed by viruses, mixed infections, fungi and bacteria. This type o f analysis underestimates common bacteria whlch respond to the usual treatment regimens. All types of immunedeficiency are characterized by decreased inflammatory responses and accordingly by the absence o r by delayed appearance of radiological signs. Included are only patients with irreversible d a m 9 of bronchial walls shown by bronchography, CTscan, histology, or i n cases of known aetiology a persistent radiological changes and matched on isotope scanning.

Six children (15%) had a congenital malformation (Willim-C a n p b e l l syndrane, absent pulmonary valve syndrane, lung sequestrations, cystic adenanatoid and harrartcmatous malformations). Six children (15%) suffered f r o m primary dyskinesia, and one child from a cystic fibrosis-like i l l n e s s , h a e v e r with negative m a t test results (otherwise CF excluded). In 11 children no predisposing factors =re detectable.

One child suffered frcm Warner-Marshall syndrcme, and ten (25%) had a history of severe pneunonia. In 7/10 Haem. influezae was cultured frcm sputun with three Ampicillin resistant strains. 

Carlsen KH, Eng J, Orstavik I . Ped i at r ic Department and M icr ob io log i c a l laboratory, UllevPl Hospital, Oslo, Norway.

FIfter acute bronchiolitis in infancy 51 children were prospectively followed until two years of age and clinically examined at all cases of respiratory infection and wheezing, and at regular control examinations at 1 , 1 112 and 2 years of age. At all occasions nasopharyngeal swabs were taken for bacteriological cultures, and at all respiratory infections nasopharyngeal apirates were drawn for virological examination by rapid immunofluorescence and cell cultures. FI virus infection was diagnosed in 68 of 158 infections examined, 31 with wheezing. Possible positive bacterial culture findigs were found in 63 of 141 infections examined, and in 52 o f 139 control examinations (P>0.2). More postive bacterial culture findings were done in otitis media than in other infections (P<0.005), but not more often in infections with wheezing, and not in children with especially frequent wheezing and infections. Streotococcus pneumoniae and Haemoohilus influenzae were the bacteriae most often isolated. Positive bacterial culture findings did not occur more often in cases with positive virological findings (P>O.2). RS virus and parainfluenza virus infections were more often related to wheezing than were influenza virus and adenovirus. The most frequent viruses diagnosed were adenovirus and parainfluenza virus. The role of respiratory virus infections in small children with recurrent respiratory infections 1s well established. Apart from in o t i t i s media, bacterial infections seem to play a minor role, and the bacteriae isolated probably represent colonisation of the nasopharyngeal space in many cases. This is an impoi-tant question for these children who often receive frequent courses of antibiotics. Dexamethasone and nebulized epinephrine reduced the symptoms and hastened recovery, b u t dexamethasone was more e f f e c t i v e by c l i n i c a l e v a l u a t i o n f o r dyspnoea and cough a t 6 and 12hours post admission. The p a t i e n t s g i v e n dexamethasone had a s i g n i f i c a n t l y s h o r t e r h o s p i t a l s t a y than those r e c e i v i n g placebo; t h e mean h o s p i t a l s t a y i n dexamethasone p l u s epinephrine group was 3 7~2 9 hours as compared w i t h 9 1~4 0 hours i n t h e placebo group (p<O.OOl). There were 3 b a c t e r i a l i n f e c t i o n s i n t h e dexamethasone groups and 2 i n t h e placebo r e c i p i e n t s . We have conducted a prospective survey of 46 consecutive cases of pertussis-like illness in children admitted to the Royal Liverpool Children's Hospital Alder Hey. Routine clinical and laboratory data was collected. In addition acute (within 2 weeks of onset of coughing) and convalescent (after 2 weeks of illness) sera and salivary samples were collected.

Using an enzyme linked immunoassay (ELISA) we have measured antibody levels (IgM. IgG, IgA) to four Bordetella pertussis antigens (LPFlymphocytosis promoting factor; LPSlipopolysaccharide, 69 kilodalton protein and FHAfimbrial haemagglutinin).

Ten patients had pertussis confirmed by culture. Of these, 6 had both acute and convalescent sera taken: all showed rising IgG antibody titre. and 4 showed acute IgM antibody, to one or more antigens. Seven culture positive cases had saliva collected: 4 showed IgA antibody to one or more antigens. 29 patients had pertussis diagnosed clinically. All 13 where acute and corivalescer~t sera were available showed rising IgG antibody titre to one or more antigen. 10 of 21 saliva samples showed IgA antibody to one or more antigens.

It appears that the measurement of salivary IgA antibody to Bordatella pertussis antigens may prove a useful t o o l for studying the sero-epidemiology of pertussis. Lxposure to irritant ynses causes inflammatory reaction o f bronchial epithelium and increased permeability for macromoleculs. This could facilitate access of antigens to immunocompetent cells of the bronchial mucosa. We studied the effect of sulphur dioxide (SO ) inhalation on local bronchial sensitization to inhaled antigens in the guinea pig.

Exposure to SO2 (0.1 -4.3 -16.6 ppm) was performed in a 20 ltr. exposure chamber f o r 8 hours on 5 consecutive days while temperature, moisture and concentration of SO were monitored and kept constant. On the last 3 days SO -exposure was followed by inhalation of 0 . 1 X Ovalbumin for $5 min. After 7 days of rest specific bronchial provocation with inhaled Ovalbumin (0.1 % ) followed by plethysmographic measurements o f compressed air (Oorsch et al., Pflugers Archiv 391:236, 1981) were performed. Specific antibodies against Ovalbumin were measured in serum and bronchoalveolar fluid by ELISA inhibition assay before exposure and at the end of investigation. The SO2 exposed group (n = 20) showed in 56 -100 % positive bronchial reactions (obstruction) to inhaled Ovalbumin, depending on the concentration of SO2, while the control group without SO -exposure (n = 12) showed no reaction (p < 0.05).

Cornpressed2air after antigen inhalation (as measurement of bronchial obstruction) was significantly higher in the exposed group compared to the control group (p < 0.001) for all SO2concentrations. Ovalbumin specific antibodies increased in bronchoalveolar fluid and serum in the SO exposed group compared to the control group (p < 0.05).

It is concluded from these results that damage of bronchial mucosa induced with low and medium concentrations of SOz facilitates local allergic sensitization in the guinea pig. The mechanisms that underly the non-specific bronchial hyperresponsiveness in asthma are poorly understood. Both an increased contractility and a decreased relaxability of airway smooth muscle (ASM) could contribute to BHR. We studied isolated ASM preparations, obtained at surgery from a non-smoking asthmatic patient with a highly increased bronchial responsiveness (PD20FEV1: 1 mg/ml histamine) and a normal lung function. The results were coxpared with those of 10 healthy controls.

The following experiments were done: (1) Measurement of sensitivity (EC50) and maximal contractile responses (Tmax) to methacholine, histamine and leukotriene (LT)C4; (2) Measurement of relaxation responses to 1-isoproterenol and forskoline, and

(3) Measurement of cholinergic and non-adrenergic inhibitory (NAI) responses to electric field stimulation (EFS). Results:

In the asthmatic tissues, the Tmax to methacholine, histamine and LTC4 was significantly higher than in normal ASM. ECSO values were, however, similar. Relaxation responses to 1-isoproterenol and forskoline of asthmatic and normal ASM were similar. EFS produced exaggerated cholinergic contractions followed by reduced NAI relaxations in asthmatic bronchi. In the presence of atropine, however, NAI responses of asthmatic bronchi were low, but fell within the 95% confidence limits of the control tissues' responses. Histological examination of asthmatic bronchi showed characteristic abnormalities, such as marked ASM hypertrophy and eosinophilic infiltration. The present observations suggest that ASX may contribute to BHR in asthma by an increased contractility, which may be related to ASM hypertrophy. AIM: To establish a met.hod to evaluate bronchial reaction in Histamine provocation test. with a minimal degree of cooperation from the patient. MATERIAL: 26 children with bronchial asthma (aged 6-15 yrs). PROVOCATION TEST: Nebulized buffered Histamine chloride was inhaled for 2 minute periods with stepwise increasing concentrations starting at 0.015 mg/ml. The total respiratory resistance ( R ) was evaluated with the forced oscillation technigue ( 4 H z ) . A resistance exceeding 150% of the preprovocation value was taken to indicate a significant bronchial reaction. Transcutaneous PO (t.c PO ) was monitored during the whole procedure with a Radiometer k M 2 monitor system. RESUILTS: When the respiratory resistance increased to 1505 o r above (mean 182%) there was a simultaneous significant decrease in transcut.aneous PO to a mean of 72% of the initla1 value. The reactionoccurredag a mean dose at 0.25 my/ml (range 0.06-2 mg/ml). The pattern of reaction was fairly uniform in the majority of children with a steep increase in R and decrease in tc Pc) , between the two last dosages.

CONCLUSIONS: Transcutangous O2 in general reacts at the same dose step as the total respiratory resist.ance in Histamine provocation tests and can thus be regarded as an indirect measure of bronchial obstruction. This technique should in particular be valuable in studying hyperreactivity in small children. and again three mnths after returning hane (October '85). There was a significant fall in total serun IgE (mean 876 to 470 iu/ml) followd by a significant rise probably biologically not relevant fall occured in IgE house mite antibdy with no rise by &to& '85.

Exercise induced fall in PEFR diminished propessively (mean 26.5 -19.2 -15.5%) and metacholine P D Z O -m 1 increased ( m a n 136 -538 -577uqn) over the n m e months, with a relapse (exercise fall 25.4% and Metacholine PD 238uqn) on returning hcme. Residence at high al68tde was associated with reduced exposure to house mites, cigarette snoke, industrial pollution and viral infections, all of which m y contribute to the maintainance of bronchial hyper-reactivity. Re-exposure results in rapid relapse in asthratic children.

(842 iu/ml)after three months at hone. A similar, but Quantitation of two domestic environmental allergens was performed on vacuum dust from the children's mattresses.

grass 70%, cat 5574, dog 61%, house dust mite 88%, Alternaria 64%, Aspergiklus 85%, Cladosporium 64%, Penicillium 94%. and for RAST was 90%. However, there was a good percentage agreement: grass 79%, cat 64%, dog 70%, house dust mite 94%, between MAST and RAST.

was a positive skin test and RAST (house dust mite, dog and cat) the MAST was negative which supported the clinical history as no symptoms were attributed to the allergens in Three more patients were negative for MAST, RAST and clinical history but had positive skin tests. compared with the MAST and RAST results in relation to skin tests. Ten patients were selected at random and the MAST repeaved. and only 4% showed a change between positive and negative results.

vitro for up to 35 different allergens.

favourably with RAST and skin test, but in some cases appeared to support the clinical history more accurately than either test in the paediatric group.

The percentage agreement of MAST with skin test was:

The overall sensitivity for MAST was 65% In 7 cases where there question.

The presence of Fel dl, Der pl and viable moulds were 85% of tests were reproducible (r = 0.977)

MAST is a simple test performed simultaneously in It compared ~s t h m a -l i k e symptoms a r e common following preterm b i r t h . Increased non-specific airway responsiveness has been described i n small groups of prematurely born children a t school age. I t s prevalence amongst these children remains unknown. determine i t s prevalence and i t s relationship t o perinatal and subsequent health.

cohort of children a t 7 years, whose birthweight was below 2OOOg. 1983; 38:760-5) t o measure the airway response t o histamine. Uoubting doses of histamine were administered u n t i l the f a l l i n peak expiratory flow r a t e (PEFR) exceeded 20% o r until a maximum cumulative dose of 6umol had been given. ihe dose required t o cause a 20% f a l l in PtFR (PDZO) was obtained by l i n e a r interpolation from the dose-response curve constructed by plotting PEFR against the log of cumulative dose of histamine. Of the f i r s t 98 children i n the cohort, 87 completed the t e s t s s a t i s f a c t o r i l y . A cohort of 110 pupils of equivalent age (mean 6.95, range 6.1 -8.0 y e a r s ) , recruited from three local schools, formed the reference population. perreactivity and precipitate asthmatic attacks. It has been speculated that asthmatic children are more prone to such infections than other children, but this is controversial. Some authors believe that childhood asthma is mainly allergic in origin.

Four groups of children with recurrent wheezelasthma ( A ) , n=59,recurrent respiratory infection without wheeze (Bln=30 neurodermitis without asthma ( N ) n=33 and a control group with no history of asthma (C)n=48 were examined for the presence of lgC antibodies against 5 important respiratory viruses.

Serum was tested by immunofluorescence and slides covered with RSV,Adenovirus and Parainfluenza type 1-3 infected indicator cells. Titersteps were measured for each virus and a mean titer for all five viruses was calculated for every patient. The mean titer was thought to reflect frequency and intensity of contact with common respiratory viruses, although an increased immunological reaction in asthmatics can not be excluded.

A clearcut age dependency of this titer was found in all patient groups with the steepest increase between age 2 and 5 . This increase was more marked and occurred earlier in groups A and B. The mean titer was si nificantl higher in A (4.89) than in C (2.96) and N ( 3 . 0 0 ) . ~p < O . O O I~. No significant difference was found between A and B (5.19).

Mean serum IgE ( % of reference values) was si nificantly higher in A (308%) and N (617%) than in C (91%) ~p<O.OOl] and B (125%) [p<O.O11 If age related values of control patients (mean +lSD) were used as cutoff points 25% of asthmatics had elevated mean antiviral antibodies only, 2 2 % elevated IgE only. and 21% both. Atopic patients without asthma ( N ) with very high IgE did not show serological signs of recurrent viral infections.

These results suggest that respiratory viral infections are relevant triggers of asthma in genetically disposed chirdren. This raises the question if asymptomatic children with genetic risk factors would benefit from the prevention of such infections. The most f r e q u e n t p o s i t i v e p r e c i p i t a t i o n t e s t s were found a g a i n s t a n t i g e n s p r e p a r e d from p i g e o n s excreta/54,5w, and from c h i c k e n , p i g e o n and duck sera /39M. The l e u k o c y t e i n h i b i t i o n m i g r a t i o n t e s t s were a l s o most f r e q u e n t l y p o s i t i v e u s i n g a n t i g e n s from c h i c k e n and p i g e o n sera. In order to evaluate respiratory impairment and the time course of recovery after thoracotomy for suspected metastatic lesions of the lung we studied lung function prior and following 24 surcial explorations in 15 patients ( 13-18 year$, Median sternotomy was chosen in 21 operations. 1-28 metastases o r suspected areas were removed mostly by wedge resection.11 operations (op) were repeated thoracotomies (2-6).

Lung function studies were performed before the operation and at different intervals ranging from 8 days to 14 months postoperatively. As expected,vital capacity (vc) proved to reflect best the loss of parenchyma and the perioperative alterations. There was a time dependant recovery of vc over 6 months up to a value of 95 % of the preoperative vc(Tab. 1 ). Repeated sternotomy,mediastinal lymph node dissection,or the number of lesions did not influence the results in a significant way. percentage of OKT8-posi tive lynphocytes (suppressor)decreases during convalescence and that this may represent a diminution of the control on IgE synthesis and a cause of the wheezing syndrome associated with the illness (Welliver 1984).To confirm this hypothesis,we studied 30 infants admitted with mild to severe bronchiolitis. The subjects ranged in age from 1 to 23 months(T:9.7?5.7);males were 17 (56.7%). In all patients T-lynphocyte subpopulations were determined twice: during the acute phase (wheezing period) and 30 days after the discharg hospital . Irachealstenosis and bronchialstenosis are relatively rare malformations in children. Treatment and clinical outcome were discussed controversially. We report on 73 infants and children with these malformations out of a group of 468 patients, in which a bronchoscopy has been undertaken between 1979 and 1983. The terms "tracheomalacia and bronchornalacia" are used if a congenital dysplasia o f a cartiiage with a pronounced collapsibility of the airway was observed. A clinical follow-up study could be realized in 54 cases. Stenosis (or malacia) was most frequently seen in the trachea (n=25) and i'n the ieft main bronchus (n=25). In 42 cases, the mucosa shows signs of a chronical inflammation, more frequent in bronchial stenosis than in tracheal stenosis. ?he predominant clinical symptoms were stridor and/or frequent bronchitis/obstructive bronchitis (n=49). In 38 cases the first clinical symptom could be abserved in the first 3 month of life, in further 24 cases within the first 12 months. Szintigraphy has been done in 51 cases and pathological resuits were observed in 49 cases. In 29 infants and children, the ventilation/perfusion disturbance was seen only in the post-stenotic area.

The analysis of the pressure/flow curves (whole body plethysmographyj revealed characteristic patterns for supra-and subglottic stenosis or rnalacia.

After diagnoses a long term treatment programme was proposed with daily inhalation of isotonic solution and with physiotherapy. Antibiotics were given in acute infections.

The clinical follow-up was excellent and Clinical symptoms disappeared in 80 % within the first 24 months after diagnosis. Diagnosis 

A fine balance exists between the inspiratory opening and closing forces controlling the patency of the upper airway. If the collapsing forces predominate, acute asphyxia rapidly leads to asphyxia1 coma and finally death. We report on a child with long-term tracheal and pharyngeal intubation for upper airway obstruction during the first two years of life. An apparently healthy newborn presented episodes of obstructive apneas during sleep, increasing in number and severity during the first 6 months of life, leading finally to repeated spells of respiratory distress, cyanosis, bradycardia, cerebral hypoperfusion and convulsions and necessitating first tracheal, then pharyngeal intubation for a period of 14 months. No signs of autonomic dysfunction were present.

The respiratory disturbances were sleep-related, more severe in supine than in prone position and not due to central causes.

The patient was successfully detubated and discharged at the age of 18 months with a normal polysomnographic recording.

Relaxation of the genioglossal muscle and/or the mandible during sleep in children might lead in certain predisposing circumstances to upper airway obstruction by collapse of the tongue against the soft palate or the epiglottis. This anatomical and physiological problem can disappear spontaneously with growing age.

In conclusion, we propose long-term pharyngeal intubation especially during sleep in infants with obstruction secondary to pharyngeal collapse : complications related to tracheostomy can thus be avoided. One hundred and three children up to 1 2 years of age underwent antrostomy in the Kuopio University Central Hospital between 1960 and 1 9 7 9 . Ninety-two of them attended for check-up after the operation, 6 years later, on average. Allergy proved to be the commonest and most important factor predisposing to sinusitis. It was the obvious cause of persistence of the condition in 50% of the children. Over half of the allergies were not discovered until after antrostomy. In 27% of the patients, the presence of nonallergic diseases favouring sinusitis had been established. One-third of these patients had concomitant atopic allergy.

After antrostomy, 3 7 % of the patients experienced no subjective symptoms of rhinitis. Only 3 % of the patients had been free from rhinitis before surgery. Forty-four per cent of the maxillary sinuses operated on, which had all been radiopaque before operation, were found to be aerated on follow-up. Seventy-four per cent of inferior meatal windows had remained patent. Sixty per cent of the operated antra were healthy, in the sense that they contained no stagnant secretion. In the remainder, stagnant secretion was observed. Secretion was highly significantly commoner (p<O.OOl) in sinuses in which the inferior meatal window had remained patent than in sinuses in which the inferior meatal opening had closed after operation.

It was evident that allergy affected the longterm results of treatment of sinusitis. In atopics postoperative rhinitis was commoner, as was the tendency for there to be stagnant secretion in the sinuses on check-up.

No immediate complications were associated with antrostomy, nor were there any serious late complications.

The Hospital for Sick Children, Great Ormond Street, London, England Stridor will be defined, and the discussion put in perspective by a brief consideration of the common causes of stridor in children, based on the experience at Great Ormond Street with 752 cases over the last 5 years.

with stridor will be presented, incorporating history, physical examination, and special investigations including eqdoscopy.

i n children with subglottic stenosis, laryngonalacia, vocal cord palsy, tracheomalacia, foreign body, subglottic haemangioma and respiratory papillomatosis.

The treatment of these conditions will be outlined in principle.

A systematic approach to the assessment of children The incidence of tuberculosis in the technically advanced countries has been declining for many years, but no such decline is apparent in most developing countries where tuberculosis remains a cause of considerable childhood morbidity and mortality.

We have undertaken surveys of tuberculosis notifications in England and Wales in 1983 and in Kenya in 1984, which provide an opportunity to compare childhood tuberculosis in the 2 countries. In England and Yales 9% of patients were children (aged less than 15 years) compared with 27% in Kenya. Nearly all the children in England and Wales were of White (48%) or Indian, Pakistani or Bangladeshi (40%) ethnic origin, the estimated annual notification rates being much higher in the latter group, namely 40 per 100,000 compared with 2.4 for the White group. The estimated annual registration rate for African children in Kenya was 30 per 100,000.

Bacteriological confirmation of respiratory tuberculosis was obtained in only 19% of children in England and Wales and 17% in Kenya; however, about half of those with a culture result were positive. A higher proportion of children in Kenya had a chest radiograph considered to be within normal limits at independent assessment, 24% compared with 10% of those in England and Wales. However, of those with a pulmonary lesion, the disease was, on average, more extensive in Kenya, 20% having disease involving a total area of more than 1 lung and 22% cavitation, compared with 10% and 5% respectively in England and Wales. In both countries lymph node disease was the commonest non-respiratory lesion and about 15% of children with a non-respiratory lesion had meningitis.

In England and Wales nearly all the children received isoniazid plus rifampicin daily, 40% with ethambutol or pyrazinamide or both drugs, the median duration being 9.0 months. In Kenya nearly all the children were treated with the nationallv recommended reeimen of isoniazid and thiacetazone daily, supplemented although many failed to collect duration. Our studies were aimed at the development of a preparation with dicreased antigenic content due to a lesser number of killed particles. A preliminary experimental study was performed in various biological test systems; controlled clinical investigations were carried out in more than 400,000 newborns. The proposed preparation, i. e. BCG-R, is intended mainly for vaccination of newborns and high risk groups of children. BCG-R vaccine contains in one vaccinating dose of 0.025 mg 500,000 to 750,000 countable particles, while one vaccinating dose of the commercial vaccine equal to 0.05 mg contains 500,000 to 1,500 000 countable particles. The use of BCG-R allows to increase the coverage of infants with vaccination by 10-12% and to reduce the number of postvaccinal complications thrice. the development of new tuberculins with higher specificity for the vaccinated organism are also of great importance. The work in this direction was started in the USSR. Thus,PPD-BCG that was proposed as a substitute for PPD but proved to be unsuitable for this purpose is now successfully used for assessing the efficiency of BCG immunization. The use of PPD-BCG in a dose of 2 TU allows to reveal 30-35% more tuberculin positive persons. Besides, the preparation gives more informative results when used for screening children of 7-8 years before the fir o t booster in j ec t i on.

agents transmission with injectors and syringes epicutaneous tests performed by means of Finn Chambers on Scanpor are preferable, They show good correlation with the intradermal Mantoux test in infants and preschool children.

In view of the increased risk of infectious Since tuberculosis is a disease that has not been controlled yet,childhood tuberculosis still represents an important problem of Public Health in our area.

We have reviewed 104 clinical histories of:children with tuberculosis as in or outpatients at this hospital during 1985 and 1986,representing 0.09% of the total number of children seen during this period and 0.83% of the total hospital admissions.

The mean age was 6 years 4 months.Nearly 50% between 3 and 7 years.Fifty three percent were male and 47% female. We have noticed a higher prevalence of endothoracic localization (79.4%) in comparison with extrathoracic forms.Exposure to a previously infected person was evident in 61.5% of the cases (50% were proved to be close relatives; father,mother or brother) .The most common clinical symptoms were fever,cough and general malaise.Thirty-five percent were asymptomatic.

Complementary examinations such as chest X-rays provided extremely valuable information in 52% of the cases.The most remarkable findings were palenchymal infiltration and hiliar adenopathy.Hematologic examinations were normal in 80% of the cases.Elevated ESR was found in 47% of them,and in 7 children with tuberculous pleurisy fluid smears were Adenine Desaminase positive.Bacteriologica1 diagnosis studies (culture and/or Zilhl-Nielssen) were positive in 15% of the studied cases.Clinica1 course was generally bening except for a case of tuberculous meningitis which had sequelae consisting in hemiparesia and hidrocephalus.

Treatment was well tolerated with almost no side effects.Chemoprophylaxis with INH was iniciated i n 36.5% of the cases.The rest received full chemoterapy with INH, rifampin and Ethambutol.Some patients had a fourth antituberculous drug or cort icosteroids administered. Duration Of treatment was from 9 to 12 months. . 10 children (30 FB) had endobronchial granuloma. All of these children received antituberculosis and gl ucocorticoisteroid(GCS) treatment. In 6/10, repression of granuloma with medical treatment alone was confirmed by FB. Amonp these, 2 had a right late t-otracheal compressive lymph hode. In 4/10, bronchoscopic resec tion was necessary(1 had a persistent bronchial stenosis). FB is a simple, well tolerated procedure even in young children. FB should be performed in all children with PT and abnormal chest Xray. FB allows a7 to determine whether the obstructive lesion is extra and/or intraluminal, b) to indicate when a GCS and/or a bronchoscopic resection should be combined with a?tituberculosis, drugs; c) and finally, to control evolution. Intra-dermal BCG vacclnatlon being stlll largely used in young chlldren (Its efficacy i s not questionable), post-vaccination complications remain a current problem. On the basls of the 1st retrospective study, we proposed a classlficatlon of serious post-vaccinal leslons and estimated risks in cohorts vaccinated from 1948 to 1974; but the number of reglstered cases was an underestlmate and the dlaqnosis criteria were not always well documented. Ti improve the notification system. we undertook prospectively a 2nd study. The group delineated t h e comallcatlons to be studled and prepared standard --_. cards for recording the diagnosis of each case. The national coordinators had to : register the vacclnated population by age, inform all the responsible speclalists, collect and check the cards to be Included in the natlonal reglster. in close connection ulth the International reglster. S i x European countries partlclpated in the new study at a national or regional level : 5 mllllon 1/2 chlldren were vacclnated from 1979 to 1981 and followed-up to 1983. The rlsks of BCG dissemlnated infections relative to new-borns (4.29 per million) and older subjects (3.58) are hlgher than those estimated In the retrospective study (1.75 and 1.95) whlch Indicates an improvement of the notification system. They are similar In the dlfferent territories. The risks of loco reqlonal abscesses (388 per mllllon in newborns and 26 in other subjects) show discrepancles In the 6 countries. probably related to the dlfferent "virulence" of the BCG substrains.

Kr'9ela K . , Galliova J. Pediatric 'FTinIE;-fFistitute for Postgraduate Medical Studies, Prague, Czechoslovakia All over the world an increased number o f BCGvaccination complications i s observed. The BCG-osteomyelitis i s a serious one and many cases are present i n Scandinevien. The interval between vaccination and symptoms in majority of cases is 7 to 24 months. The pathological finding is frequent limited to one bone. oft it is sternum, clavicula, ribs, long and small bones of limbs, not so oft spine and flat bones of skull and pelvis. The diagnosis is proved histologically, in about one hbPf of cases bacteriologically, tc.0.

In Czechoslovakia the BCG-osteomyelitis w a s not observed till 1980. From this year a new vaccine with a higher virulence i s used. I n the last 6 years we have cured 28 cases. I t represents a n incidence o f 3,5/100.000 vaccinated newborns. 19 cases are boys, 9 cases girls. Except two a l l w e r e vacci-nated after birth. The interval between vaccination and first symptoms was 10 t o 41 months, on the average 17,8 months. I n most cases one bone w a s affected, in two cases there were 2 bones. I n 9 cases it w a s femur, in 6 cases tibia, in 4 cases humerus, i n 3 cases spine, i n 2 cases sternum and calcaneus and in 1 case fibula, tarsus, rib and finger. The diagnoeis was proved in 25 cases histologically, in 9 cases the BCG stem was standardised. The tuberculin test w a s in all but one case positive 6 to 22 M M in diameter, on the average 13 MM. Immunodeficiency w a s not proved in our patients, but w e cannot rule out some defect o f the local immunity, because i n most cases the reaction on the vaccination place w a s very small o r absent. A retrospective study on mycobacterial cervical adenitis among Finnish children in 1977-86 was performed to gain information on incidence, etiological mycobacteria and clinical data of the disease. The material was based on the tuberculosis register of the National Board of Health and on the records of the reference tuberculosis laboratory**. The number of cases registered in the 10 year period was 33, with 25 girls and 8 boys, which gave an incidence of the order of 0.3 cases / year / 100 000 children. Lymphadenopathy had mostly developed in connection with upper respiratory infection tonsillits or otitis, but when taken to examinations, the child ren lacked signs and symptoms of infection. In all cases, the diagnosis was based on histopathological changes typical of tuberculosis. Microbial cultures of the biopsy material were positive for mycobacteria in 40%. Atypical mycobacteria, predominantly M. avium-intracell ul are, outnumbered tuberculosis by 1 to 10 as etiological microbes. A wide local excision of the affected lymphnodes seemed to be the therapy of choice. Antituberculous drugs seemed to be of little value in treatment of atypical mycobacterial infections.

born. Tuberculin tests by Mantoux technique were positive in 50% of the confirmed cases with atypical mycobacteria and in 28% of the cases based on histopathology alone. Neonatal BCG vaccination seemed to protect children against atypical mycobacteria, especially at 1-4 years of age. A comparison to Swedish data on cervical adenitis due to atypical mycobacteria confirms this observation. The importance of atypical mycobacteria as etiological pathogens has to be recognised. Contrary to tuberculosis which always has to be treated with specific drugs, atypical mycobacterial infections need proper surgical excision of the affected lymph nodes, which preferably is performed in connection of the primary biopsy, and antituberculous drugs are needed only exceptionally. Studies evaluating adverse effects of oral T on learninglbehavior have been performed on children with asthma receiving chronic T therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6-12 yrs) who had not received oral bronchodilators for at least 6 mo. A double blind, placebo(P) controlled, parallel format was used with a 4-week T or P period preceded by a 2-week baseline. T serum levels were maintained between 10-20 ug/ml. child's home and school behaviorlperformance were monitored independently by their parents and teachers using standardized report forms. A battery of psychological tests was administered at the end of baseline and treatment periods. All children receiving T were noted to have a change in school behavior/performance during their 4 weeks on drug compared to baseline, while none of the children receiving P were noted to be different (p=.004). Benton Visual Retention Test (memory) results were abnormal during T therapy (p<.O5).

Thus, the short term administration of T to asymptomatic asthmatic children previously off chronic oral bronchodilators can adversely affect school performance, behavior and memory. Since this population represents the majority of asthmatic children, one needs to use T cautiously in this age group, monitor school performance closely, or seek other treatment modalities. Hospital admissions for childhood asthma have increased markedly in recent years, despite advances in treatment. In 1986, 820 children made 1389 visits to the AED at RLCH Alder Hey for acute asthma. To investigate reasons for repeated attendance, those who came twice or more in 12 months were assessed by questionnaire and , in those > 5 yrs, interval lung function tests ( L F T s ) , and compared with a control group 14470).

10 of these children with mcderate to severe as-were being chronically under-treatd, whilst a f'urther 5 children, whose control deteriorated 3 to 6 mths before death, did not receive appropriate changes in therapy.

of OPD asthmatics who had nor needed emergency treatment for a least 12 months.

LFTs showed lower mean FEV1 !79% vs 84%, p<O.O5), Vmax 75-25%VC (48% vs 59%, p<O.Ol), Vmax 25% VC (56% vs 70%, p<O.O5) and FEV,/FVC% (75 v s 79, ~<0.005) in AED children. Mean iii) Delayed referral to hospital: 12 cases (Z.?',) .

In the mjority of cases, parents had not been given clear advice on rht to do in a severe attack.

iv) Shoptirral r r a~g a n e n t of the final illness in hospital: 7 cases (mh).

If btwe deaths are to be prevented, greater efforts need to be mde to alert all parents to the potential danger of acute or deterioratbg asth. 'hey should be given the means to initiate w l y treatment with oral corticc-steroids and to maximise bronchodilator therapy. Tney should be given clear guidelines as to when to seek help. Measuring bronchial reactivity by cold air challenge(CACh) is the prerequisite for assessing the "functional dimensions" of childhood asthma. TWO girls with asthma, 1 0 and 1 4 years old, died suddenly in the winter 1 9 8 5 / 8 6 . Both had been classified by clinical criteria as moderately severe asthma, had given the impression o f a well-stabilized disease course, and h a d shown good compliance with regular antiasthmatic medication. By chance, bronchial reactivity had been assessed b y the above method and concept within the last 6 months before death in both cases. For comparative purposes, we then assessed the "functional dimensions" in 37 children with asthma o f the same clinical severity. Consequently, measurements from the two index cases can be compared to those from this group. Baseline lung function of the two girls was on t h e lowest end of the group spectrum: the "functional optimum", measured after bronchodilator medication, was also below average f o r both index cases. The "functional minimum", defined as that level of lung function measured at maximum reaction after CACh, was again in the lowest end of the group spectrum. The "range of reactivity", defined as the distance between optimum and minimum, was of average dimension. In addition t o lung function measurements, the children scored their subjective feeling of "chest tightness". A perception score, relating subjective perception and lung function impairment, was calculated. This score, applied for the situations of baseline lung function and post-CACh minimum, was markedly below average for both index cases. In summary both girls with later occuring sudden death demonstrated a h i g h degree of reactivity, only partial recovery of function after bronchodilator, and a markedly r e d w e d perception of bronchoconstriction. change in PEFR was greater on exercise (39% vs 33%, p<O.O5), bronchodilator (31% vs 26%, p<O.O2) and lability index (47% vs 381, p<O.O2) in the AED group. had worse "worst ever" attacks (34% blue v s 14% OPD, p<O.O5).

There were no differences in treatment; 97% AED, 99% OPD Usual attacks were of equal severity, but AED children had a bronchodilator at home, 73% AED, 68% OPD took prophylaxis and 11% AED and 12% OPD had a home nebulizer.

Parental knowledge was similar. 73% of AED and 71% of OPD parents thought asthma could be fatal, but 71% of AED vs 56% OPD had feared their own child might die (p<O.O5), and would seek medical help sooner (p<0.005).

Repeated attendance for asthma is related to greater severity of disease and parental concern, but not to differences in treatment, ignorance or social disadvantage. Airways (OA) and Living with Asthma (LA) was planned to compare these programs systematically. Because both programs are long, we decided to compare the full length programs with version shortened to four sessions, to explore the possibility of making them less costly to deliver and easier for families to attend. 14 University-based Pediatric Research Centers were matched for region (North, Central, and South) and randomly assigned to deliver either OA or LA. Each Center was to offer the complete version first (Phase I), enrolling 20 families (10 experimental (E) and 10 control (C)), followed by the shortened version (Phase II), for which an additional 20 families would be enrolled. The participants were stratified according to age (7-14) , severity of asthma (3 13vels) and gender and randomly assigned to E and to C group.The design called for pre/post measurea of knowledge (k) , morbidity and physiologic parameters of FEVl and reversibility and a I-yr follow-up period with bimonthly physiologic measurements. 368 families were enralled in the study (190 E and 78 C; 248 in Phase I and 123 in Phase 11) with a participation rate of 85% for children, 87% for mothers and 54% for fathers. Improvement (mean % change of correct answer) in asthma knowledge .observed in mothers was 8 in "theoretical," 10 in "factual" and 4 in "behavior" k. For children the mean % improvement was 27 for both "preventive" and "management" behavior (all stat. sign. increases beyond p<0.05). await results of the follow-up yr. Pediatric Clinic, University "La Sapienza," Rome, Italy; * Buffalo NY, USA; **2nd Pediatric Clinic, Bologna, Italy. We performed a study to determine in which way aocio-cultural level of the family and the severity of asthma can influence the acceptance of ASM program in two non-industrialized regions. In the first region a population of 5817 children 6-15 was surveyed by question.through the schools. The response rate was 91% (53081, 2.5% ( 1 3 4 ) Ronchetti ft. 4th Ped.Clin. Univ."La Sapienza"R0ME.

Exercise Induced Asthma (EIA) is a very frequent clinical. problem 1.n asthmatic children. Its prevention is important in order to assure these patients of as nearly normal life as possible. The present study was undertak:en to determine the bronchodilation and EIA-preventive effect of oral Clenbuterol (UCL) and inhaled Clenbuterol (ICL) (dose .1 m c g / K g ) .

We studied 12 children, aged .11.6f0.5 SE, 9 M and 3 F,affected by E I A (previous positive exercise test).

The patients performed 3 standardized treadmill exercise tests in 3 different days, 240 minutes after OCL or I C L or placebo (PL) in a double blind randomized manner.

Flow-volume curve parameters, arterial blood pressure and heart rate were tested in basal conditions

. . search was carried out in a comparable region where 2417 children were surveyed. 85% (2059) responded and 2.3% ( 4 8 ) had an asthmatic episode during the year. The 1st interview was skipped and combined with the 2nd interview. The response rate was 50% ( 2 4 ) ; these children were divided into two groups: E=14 and C=lO. The children who followed the whole program asthma and were brought up in a higher socio-cultural environment than children who dropped out. Short-term outcome measures demonstrated statistically significant improvement in k for all. The results demonstrated that ASM programs may have t o face not only financial, but also socio-cultural obstacles in the recruitment of subject. Probably different strategies are needed to induce those who need it most t o participate and to increase attendance at ASM programs.

were affected by a more severe In 27 children, aged 2-12 years, hospitalised with acute asthma, changes in oxygenation and heart rate when nebulised salbutamol was driven by compressed air and 100% oxygen were compared in a randomised crossover study. saturation (Sa02) was monitored using a Biox 3700 pulse oximeter for 5 minutes before, during and for 15 minutes after nebulised salbutamol 0.15 mgs/kg (max of 5 mgsl.

Pretreatment SaOZ was similar for both treatments with means of 92.0% (air) and 91.9% (oxygen). Oxygenation improved in all patients while receiving nebulised salbutamol driven by oxygen (mean increase 6.0%. p<O.OOl).

During treatment with compressed air, the mean change for the group was +O.p3% bq't 4 patients showed a fall in Sa02 of at least 2%. Five to 15 minutes after treatment, Sa02 fell by at least 2 % in 8 patients; 5 after compressed air only, 2 after oxygen only and 1 after both treatments.

The fall was at least 4% in 4 of these patients, 3air and 1oxygen.

fell asleep during or after treatment compared with 2 that received oxygen, ~0 . 0 3 9 .

Pretreatment heart rates were similar for both groups with means of 125.9/min (air) and 122.6/min (oxygen). Heart rate increased during treatment with compressed air and after both treatments, ~(0.01 but did not change during treatment with oxygen, p > 0.5.

In all, 10 children showed a drop in SaOZ of at least 2 2 during and/or after nebulised salbutamol. demonstrates that using 100% oxygen rather than compressed air as the driving gas prevents the hypoxia and tachycardia that occurs during administration of nebulised salbutmol in some children. We have previously demonstrated that the majority of young asthmatic children are hyperinflated even when asymptomatic.

We have subsequently studied the effect of an inhaled steroid on lung volume in asthmatic children aged 2-6 years with frequent symptoms. The trial was double-blind and after a two week "run-in" patients were randomly allocated to receive either budesonide 20Oug or placebo twice daily via the nebuhaler for 6 weeks. Functional residual capacity (FX) was measured by helium gas dilution before and after the treatment period and expressed as a % predicted for height.

Results are available on 23 children, mean age 4.6 years; 13 have received budesonide and 10 have received placebo. In the majority of children FRC was increased before treatment; the mean FRC was higher in the budesonide group (1402, range 96-1692) than the placebo group (123%, range 97-155a). This did not reach statistical significance. The change in FRC after budesonide (mean -17.1%) was significantly greater than after placebo (mean +4.22) p < 0.05 (Wilcoxon rank sum test). The For successful post-natal pulmonary adaptation some minimum requirements are necessary,including: initiation of regular, rhythmic and controlled breathing pattern; rapid resorption of fetal pulmonary fluid combined with the establishment of a normal alvelolar lining layer; development and maintenance of proper static and dynamic pulmonary mechanics to permit easy ventilation and sufficient gas exchange; and establishment of a physiologic ventilation-perfusion relationship. This presentation will focus only on neonatal pulmonary mechanics.

The purpose of studying respiratory mechanics is to measure elasticity and frictional resistance, as well as airway resistance, in the thoracopulmonary system. It is important to analyse whether airflow in the individual parts of the bronchopulmonary system is uniform OK not, and whether relationships between elasticity and resistance vary from one area to another. Knowledge of these functional values in the neonatal period (birth until age 4 weeks) not only increases diagnostic opportunities but also assists early indication for appropriate treatment, and the critical assessment of treatment results. In the immediate postnatal stage, analysis of respiratory mechanics also offers the possibility of showing the functional state of the surfactant system, and provides information about fluid resorption in the lungs.

Furthermore, the study of neonatal respiratory mechanics is an integral part of research on the respiratory distress syndrome (RDS). Such studies (postnatally and under spontaneous or artificial ventilation) enable objective assessment of the action of substances (administered both in utero and immediately after birth) that affect the surfactant system, or assessment of changes in pulmonary mechanics following surfactant instillation.

Lindroth, De t of Paediatrics, University Hospital, Lund, Swezei. Several follow-u studies have reported fre ent respiratory probyems growth retardation a n r retarded psychomotor'development in BPD-patients .

In a long-term follow-up stud up to the age of 10 ears we have followed $ 8 Pow birth weight inf a d s surviving after ventilator treatment in the newborn periode. Fourteen hag BPD. Pulmona mechanics shortly after ventilator treatme2 showed low compliance and hi h resistance examination one year later s%owed normalizaffon in both parameters. However at the age of 10 the BPD-patients in many resbects showed si ns of im aired lungfunctions e.g. abnormal F d l , FRC anz VTG. Lower respiratory tract disorders were common in many BPD patients during the first two years but later subsided. Weight and length develo ment were retarded during the first years but at tge a e of 6 the patients had normal rowth All atienzs were tested with Griffith &velo.menta? test. The BPD-and non-BPD patients did noe differ from a normal population. However, clumsiness and concentration difficulties were relatively common in both groups. Treatment of BpD differs in the acute and late phase. When.stil1 on ventilator the patient shall receive optimal ox genation with lowest pQSSible peak pressures. Pagent ductus arteriosus is a common complication and often needs Jigation.

dose are sometimes useful in deteriorating B8Dpatients but as often have no effect Moqt of of the mbntioned drugs however have'serious side-effects which will be disc6ssed. A multiple breath nitrogen washout method was developed t o study lung function in very low birth weight infants (< 1 500 g) during ongoing mechanical ventilation. To measure ventilatory flow, the baby was placed in a whole body plethysmograph with i t s face outside. During an expiration the breathing gas was instantaneously changed t o 100% oxygen, w i t h maintained respirator setting, and the nitrogen washout course was followed. By computerized methods the functional residual capacity (FRC), nitrogen elimination pattern (distribution of ventilation) and nitrogen clearance were calculated. The use of body plethysmography also enabled simultaneous measurement of lung mechanics.

So far, five VLBW infants requiring mechanical ventilation longer than during their first month of l i f e were studied repeatedly.

During mechanical ventilation there was a progressive increase in FRC i n combination with an increase in lung resistance (R1). The nitrogen clearance was also increased.

We conclude, that the changes in FRC, nitrogen washout course and RI reflect a progressive airway damage in infants developing BPD. Improved antenatal ultrasound facilitates both diagnosis and treatment of fetal abnormalities.

Pleural effusions may now be diagnosed early in gestation and this raises the possibility that chronic drainage by pleuro-amniotic shunting may allow normal lung growth and reduce problems at resuscitation.

We describe 9 cases of antenatally diagnosed pleural effusion k hydrops fetalis in whom pleuro-amniotic shunts were inserted, gestations from 24-35 weeks ( 2 cases were bilaterial).

In all 9 cases there was successful drainage of the effusion without fetal distress.

In 2 cases the effusion reaccumulated two weeks later, following probable fetal removal of the shunt, further shunts were inserted. One infant delivered 24 hours after the second shunting procedure at 30 weeks gestation, she developed respiratory distress syndrome but had no pleural effusion at birth. One infant delivered 6 weeks after shunting (35 weeks gestation), required minimal resuscitation but later died of pseudomonas septicaemia, there was no evidence of pulmonary hypoplasia at postmortem examination.

The remaining 7 infants delivered between 35-40 weeks, requiring minimal or no resuscitation and none required drainage of pleural effusion postnatally.

At follow-up there were no respiratory problems.

In B infants measurements of lung function demonstrated normal lung growth. The infant delivered prematurely who had respiratory distress syndrome initially had low lung compliance but when seen at 1 year of age had functional residual capacity within the normal range.

These preliminary results suggest antenatal insertion of pleuro-amniotic shunts results in chronic drainage of pleural effusions reducing problems at birth and permitting normal lung growth. but conventional antihistamines only weakly antagonize its effects at bronchial muscle H receptors; they are not therapeutically beneficial because of sedative and other side effects. devoid of side effects. We have investigated the effects of histamine blockade by terfenadine on resting bronchial tone and EIB in a randomized double blind placebo controlled trial. Twenty children (5.5-14.8 years) were studied on 2 days 48 hours apart, by PEFR and FEV measurements for 3 hours after oral placebo o r terfenadine AOmg, followed by a free running exercise test. Baseline values were the same on each study day. Terfenadine induced significant bronchodilation within 1 hour of ingestion when compared with placebo and a 32% improvement in FEVl by 3 hours (p<O.OOOOl) increasing FEVl from a baseline mean % predicted 69% to 84% by 3 hours. The degree of bronchodilatation showed a significant inverse correlation with baseline FEV (r=0.81, p<O.O0005). After 1 exercise challenge terfenadine significantly inhibited EIB (terfenadine 21.5% fall PEFR, placebo 32% fall, p<O.O37), but when the exercise test values were normalized to the placebo baseline to eliminate the effect of prior bronchodilatation, no such protective effect was evident.

Selective H blockade using terfenadine has an acute bronchodilator ekect suggesting that asthmatic children have significant resting 'histamine tone'. The inhibition of EIB by H blockade is a non-specific effect of its bronchodilator propirties rather than a separate effect on bronchial reactivity. asthma cannot be inferred from this study. Twenty-five asthmatic children aged 5-14 attended the respiratory laboratory for routine pulmonary function testing. The children had refrained from using bronchodilators for at least four hours prior to testing. We measured thoracic gas volume and airways resistance in a whole body plethysmograph, and performed routine spirometry. We then recorded a cough sequence from all subjects. Each child was seated, wearing a noseclip, and breathing quietly through a pneumotachograph. When the end-expiratory level was stable, he inspired fully, then coughed out as forcefully as possible to residual volume without intervening inspirations between the individual cough efforts. Signals of flow and volume were stored and subsequently plotted at t speed onto an X-Y chart recorder.

Each child then took his routine dose of bronchodilator and all measurements were repeated 10 minutes after medication. The flow-volume profile of each cough effort showed a rapid rise in flow to a transient geak, followed by a period of lower flow rate equivalent to that during a forced expiratory flow-volume (FEV) manoeuvre at the same lung volume, and finally a return to zero flow during the period of glottic closure prior to the next cough effort.The efforts fell in a straight line and were joined by eye. For each subject we calculated the cough ratio as the ratio of maximum expiratory flow(MEF)(equivalent to that obtained in the FEV) to transient peak flow obtained during coughing, at functional residual capacity (FRC). We found that following bronchodilator there was an increase in maximum expiratory flow rates, and a proportionally greater increase in cough peak flow. relaxationof sronchial smooth muscle and an increase in airway cross-sectional area. This would increase maximum flow rates (according to wave speed theory) both for maximum expiratory flow and for cough. In addition, bronchodilators would increase airway distensibility, which would lead to a fall in expiratory flow rates. We suggest that the different magnitude of change in maximum expiratory flow and cough peak flow caused by bronchodilator is brought about by differences in the relative influences of these two factors. Ijebulised beta-2 adrenoceptor agonists are still used in the treatment of infantile wheezing in spite of the evidence that they nay be ineffective. Lie have recently shown that they may cause deterioration in peripheral airway function (Prendiville A, Green 5, Silverman 14. Paradoxical response to nebulised salbutamol in wheezy infants assessed by partial exoiratory flow volume curves. Thorax 1987; 42:86-91). and airway calibre in response to nebulised salbutamol in recurrently wheezy infants.

Nebulised saline Z5ml and preservative free nebulised salbutanol 2.5mg were given to 5 recurrently wheezy infants on nine occasions. Changes in oxygenation(measured by pulse oximeter Ohmeda Biox 3700 and transcutaneous PO2 monitor Kontron Cutan 820) and PCO2 (Radiometer TCM 20) were measured in the five minute interval prior to and at 0-5 and 15-20 minutes after saline and salbutamol administration. A significant mean drop in Sa02 of 2% (pd.01) and Ptc02 of 1.3 kPa (pUl.001) was seen at 0-5 minutes after salbutamol administration. The maximum drop in SaU2 of 4% and in Ptc02 of 1.8 kPa occurred at a mean time of 11 min after salbutamol. lwenty min after the end of nebulisation, the mean value of Ptc02 of 7.1 kPa was still significantly lower than the mean value of 8.4 kPa pre salbutamol administration (pUJ.01). were no significant changes in PtcC02. Nebulised saline had no significant effect.

This study shows that hypoxaenia, lasting for at least 20 min, can follow bronchodilator therapy. Because of its duration, the effect is unlikely to be due simply to the pH or osnolality of the preparation. In 13 asthmatic patients however, with the same degree of lung function impairment, they did not find any correlation between trapped gases and other parameters of hyperinflation and of airflow limitation. We therefore decided to check these relationships again in a small pilot study with 13 asthmatic children and found good correlations between trapped gases(in % of TLC = TGXTLC) and TGV(r=0.785,p<001) as well as RV(r=O.718,pc.Ot). for confirmation of these results we increased the number of patients to 54 and found these correlations still significant, although much weaker (TG%TLC/TGV r=0.382,~.01; TG%TLC/RV r=0.363,pr.01). We also got significant correlations between MEF50 and RV(r=0.443,pd.001) ,and MEF50 and TGV(r=0.323,pc.01), whereas there was no relationship between the parameters of airflow limitation and air trapping. Preliminary analysis could not define significant differences between the pilot study group and the whole group of 54 patients. However the ongoing study includes clinical parameters to find out subgroups o f asthmatics with a very good or no correlation between the lung function parameters mentioned above. children) during the night was assessed. Studies were performed on three nights for each child. Ambient temperature and relative humidity were recorded every five minutes throughout the night on a Grant Squirrel Data Logger. A voice-activated system with electronic time signal recorded cough. Sixteen children coughed on 44 nights with a median of 6 bouts of coughing per night (range 0-272). The cough rate in the two hours after going to bed was significantly higher than the cough rate in the middle of the night (2-4 a.m.)(p<O.Ol). Peak coughing times were 7-9 p.m. and 6-8 a.m. The mean ambient temperature in the chidlren's rooms was 18.4OC (+2.1°C). The minimum temperature occurred between 5 and 7a.m. There was great variation from room to room in relative humidityovernight median 53% (range 26.5-68%). There was no significant alteration in cough rate during periods of either rapid temperature change (>l°C per hour) or rapid change in relative humidity (>2% per hour).

The timing of night-time cough observed in this study differed from the known bathophase of circadian Cycles described in adults and children. The interpretation and possible therapeutic implications of these findings are discussed. To investigate whether chronic airways obstruction stimulates secretion of atrial natriuretic peptide (ANP) we measured plasma ANP levels in 24 consecutive asthmatic children (group A, mean age 7.9 yrs, range 4.6 to 15.7 yrs) compared to a control group of 19 healthy children. Blood samples were taken from 8.30 to 12.00 a.m. in the recumbent position after a normal breakfast. ANP was measured by direct radioimmunoassay (RIA) from unextracted plasma as described earlier.

In addition, plasma aldosterone was measured in 19 asthmatic children with a commercially availiable RIA (DPC) .

In Group A, mean ANP levels were increased compared to normal children (180 vs. 124 pg/ml, p=O.Oll). Mean plasma aldosterone concentration was 253 pg/m1 (range 50 to 932 pg/ml) in asthmatic children. There was a strong correlation between ANP-I and aldosterone (r= 0.70, p c 0 . 0 0 1 ) . Small airways obstruction measured by trapped gas was associated with higher ANP-levels (r= 0.44) and lower aldosterone values (r=0.76 with l/aldosterone, ~~0.01). Moreover, there was a positive correlation between aldosterone and serum IgG (r=0.61, ~~0.01). These resultssuggestthatchronichyperinflation leads to ANP secretion, probably by increasing right atrial pressure. Lower aldosterone levels can be explained by the inhibitory effects of ANP on the reninangiotensin-aldosterone axis. The clinical implications of these observations for the treatment of asthmatic children remains to be determined. During an epidemiologic study of respiratory health, 554 children (aged 6 to 15 years) attending three schools in Pisa (Italy) were enrolled. Sixty-seven of them refused to participate to the study.

Remaining 487 children answered a questionnaire on respiratory symptoms and underwent pulmonary function tests (PFT) in baseline conditions and 10 min after the inhalation of 200 mcg of salbutamol. PFT were considered acceptable when at least 2 trials were obtained in which FEVl differed by 5% or less both in baseline and post-salbutamol sessions; accbrdingly, PFT from 127 children that did not meet this criterion were excluded from analysis. Three-hundred-three children, among those with acceptable PFT, were considered normal on the basis of absence of past and present respiratory symptoms. Change in FEVl after salbutamol was calculated as the difference between prebronchodilator and postbronchodilator highest values divided by the pretest value and multiplied by 100. The mean change resulted 1.37% + 0.31 (SE). This change showed highly significant by paired t-test ( p < .001). Since the distribution of values was not normal (skewness = -.55) we used the 95th percentile method to define upper normal limits: 95% of normal children had a change in FEVl lower than 9 % . In conclusion, a bronchodilation test with salbutamol should be considered positive when a change of 9 % or greater in FEVl occurs. Gotti. Pediatric Clinic, University of Pisa, ITALY.

"ITALIA PROJECT" is a multicenter study on selfmanagement in childhood asthma conceived to assess the effectiveness of different programs in italian children. At the University of Pisa the program "living with asthma" was tested and its original form ( 8 lessons) was compared with a shortened form (4 lessons). Thirty-six children, aged 7 to 14 years, and their parents entered the study: ten families were assigned to the original course, 8 to the shortened form and 18 to the control group. The severity of asthma was assessed in baseline conditions: children and their parents answered a questionnaire on knowledge about asthma; parents also answered a questionnaire on anxiety. Lessons were delivered by physicians separately for children and parents in 8 or 4 weeks for long and short course, respectively. The same questionnaires were administered at the end of course. A complete reassessment of severity of disease, level of knowledge and anxiety is planed at the end of a 1 year follow-up period (april, 1987) . Preliminary results indicate that the baseline knowledge about asthma is rather high both in children and in adults (about 30% and S O % , respectively). At the end of courses the improvement in knowledge was similar for the two experimetal groups and showed inversely related to the baseline level; no substantial improvement was shown in the control group. same beneficial effect may be obtained in children below the age of two years, suffering from repeated attacks of bronchopulmonary obstruction after an initial attack of bronchiolitis.

Admitted to the trail were children below the age of two years who had had one attack of bronchiolitis previously and afterwards suffered at least from one episode of bronchopulmonary obstruction. The children wdre randomly allocated to receive either placebo or beclomethasone dipropionate solution given in a nebulised form. This was given over an eigth week period,and the patients were followed up for one year. The results showed that the placebo-group(P) during this year had more respiratory infections, more bronchc pulmonary obstructions and used more symptomatic treatment than the group receiving active treatment(B). The two groups were matched in all respects except that children in P-group were somewhat older than those in the B-group.

dipropionate given in a nebulised form influences the number of respiratory infections children contract after an initial episode of bronchiolitis. And it also influences the number of bronchopulmonary obstructions they get after the initial bronchiolitis. I n a l l subjects it has been made spirometric controls and a bronchial provocation t e s t with carbachok a t the s t a r t and each two weeks untiZ the end of the study.Parents have recorded a daily clinical diary on the asthma symptoms.

I n both groups it has been an almost identical improvement of non specific bronchial reactivity .(p<O.OOl 0-12 weeks1,contemporary t o the reduction of asthma symptoms.

Endingpit is possible t o affirm that both drugs are efficacious t o reduce,for a medim time treatmnt,the m n specific bronchial reactivity,perhaps for an " a n t i a l k r g i c " action,as a consequence of the inhibition of the release ofrmstocitary primary and secondary mediators. and of the flogosis by them induced. visaged as a mechanism capable of limiting the bronchoconstriction introduced by hypoxia and hypercapnia, i.e., a mechanism for optimizing the conflicting influences of dead space and airway resistance on alveolar ventilati01-1.~~ It should also be noted that the neuromuscular mechanisms controlling airway tone are less effective in the newborn." In the adult the majority of vagal respiratory fibers originating from the lung and airways are unmyelinated, the ratio of unmyelinated to myelinated fibers being 11 :l .78 The mechanosensitivity of these receptors, and thus any clear modulation of their activity during respiration, is more difficult to demonstrate due to a higher Ptp threshold than that of the SAR and RAR.",'O The properties of these receptors are usually studied by stimulating their activity with extraneous substances like capsaicin and phenyldiguanide. As yet little is known about the location of these endings, although some have been found to be directly associated with the airways.'' 'Iho groups of C-fiber receptors have been distinguished on the basis of their circulatory accessibility: "pulmonary" receptors, which, after injection of a challenging drug, are reached with shorter latency periods via the pulmonary vs the systemic circulation and "bronchial receptors," which are reached with shorter delays via the systemic vs the pulmonary circulation. Another difference between the two groups of endings is the relatively greater mechanosensitivity of the "pulmonary" endings, which have a lower Ptp t h r e~h o l d .~~.~~ These receptors might be identifiable with the J receptors of Paintal." An interesting feature is their different chemosensitivity to extraneous or naturally occurring substances. Among the latter, bradykinin, histamine, serotonin, and prostaglandins (of the F or E series) stimulate "bronchial" C-fiber receptors, while only prostaglandins of the E series stimulate "pulmonary" C-fiber endingsE0 At present there are no specific data for corresponding receptors in the newborn. bronchial responsiveness. Such bronchial hyperreactivity may lead t o airway obstruction which a t one extreme is easily reversible and a t t h e other is only partially reversible. Clinical asthma is characterized by smooth muscle contraction, hypersecretion and mucosai swelling.

Two main mechanisms leading t o airway obstruction a r e recognized. Neurogenic mechanisms produce obstruction either by direct reflex action or as a result of abnormalities in t h e non-adrenergic non-cholinergic system. The other major mechanism is the release of mediators from sensitized cells. A further mechanism, mucosal inflammation in the airways is in many cases related t o the other two, but can occur independently.

A popular scheme for t h e pathogenesis of asthma suggests, that epithelial damage exposes afferent nerve endings in the airway epithelium which become irritated by mediators released from inflammatory cells. Stimulation of these nerve endings causes a variety of effects icluding smooth muscle contraction, leakiness of the bronchial vessels and mucosal hypersecretion.

The number of inflammatory cells in the mucosa seems t o correlate with asthma severity, is increased during t h e late stage of the asthmatic reaction t o bronchial antigen challenge, and is raised in necropsies of patients that hade died in an asthma attack.

To conclude in the pathogenesis of asthma t h e emphasis is put on t h e neurogenic mechanisms and the inflammation of the airways. These mechanisms may be of great importance, because they may have implications for the treatment of t h e disease. It seems that t h e bronchial inflammation of asthma patients should be treated a t early stages of t h e disease more vigorously than it is done a t present. The definite etiological diagrosis of bacterial pneLmxlia in children can tE achied only by isolation of bacteria frm blocd or lulg aspirate. Wver, blcod cultures are psitive only in a very few patients ard invasie tedniques like lun~ palcture canrot k recarmJldgf for Mitw use. l?emxcccus (FK) i s considered to be the mst ~m r n causative kteriun toth in children a d adults and the dsranstration of PNC antigen in the sprtun obtained frun adults with m i a has b m s h to tE a useful tcol for rapid diagnosis. In the present study w wanted to investigate, if the dennstration of P X in nasotrackal aspirates (NTA) cwld tE used for the rapid diagnosis of PNC W i a in children.

M A sanples, collectej by suction thm@ a catheter inserkd thrwJh a nostril so deep that it elicited a vigorous cough reflex, WE 0btair-d f m 1% children (1 rrarrth to 6 years of w) with Xray positive p7eLnmia. PNC antigens wre deteded in the M A smples by colnterimnnoel&mresis ard latex agglutinatim. PK antigen was f w d in 30.5% of the M A smples studied. khen PNC antigen findings wre correlatd to CP-concentrations in t k acute sera of these children, PNC antigen was pxitive in 16% of M A specims of children with C P 40 ng/l (probably m-bacterial p-mmia) ard in 46.5% of those with CRp fl q/l (probably bacterial). The results wggest that P K antigen-&Wion as an only diagmstic test is not suitable for etiological diagnosis in individual patierrts. tbwver, khen canbir-d with a hi@ CP-level, it is suggestive of PK etiology.

Departments of Pediatrics and Virology, Turku University, Turku, Finland

Since 1980 rapid diagnosis of respiratory virus infections (adeno-, influenza A and B, parainfluenza 1 , 2 and 3 , respiratory syncytial viruses) have been extensively tested in Turku. Indirect radioimmunoassay, enzyme immunoassay and recently time-resolved fluoroimmunoassay have been used to detect the virus antigen in the nasopharyngeal mucus. Currently used fluoroimmunoassay permits the diagnosis in 60 minutes. During 6 years 4524 nasopharyngeal mucus samples were taken in the Department o f Pediatrics and 903 p~royeh to be positive ( 2 0 % ) . Most common infections were RSV, adcno-and parainfluenza 3 infections. Separate studies concerning the clinical value of rapid diagnosis have been carried out. In febrile children, tonsillitis and acute otitis media rapid diagnosis was positive in 2 0 -3 0 % of the cases. However, in wheezy bronchitis rapid test was seldom positive since the illness was most often caused by coronaviruses and rhinoviruses. During 1986-87 influenza A epidemic the clinical practicability of time-resolved fluoroimmunoassay was tested. 160 nasopharyngeal samples were tested and 30% were positive.

We conclude that rapid diagnosis of respiratory virus infections has a great clinical value. The influenza A and RSV epidemics can be rapidly recognized. Spesific etiologic diagnosis of highly febrile children should have marked influence when the necessity for antibiotc therapy is considered. Fiberoptic bronchoscopy is widely practiced in adults under sedation, without the need for a general anaesthetic. In children a general anaesthetic is required which removes one of the major advantages of this method. The size of the bronchoscope reduces the available tracheal leumen for anaesthesia and the 4 . 9 mm fiberoptic bronchoscope is only suitable for children down to approximately 29 years old. The main advantages of the flexible bronchoscope is its manourverability. The upper lobe bronchi are easily visualised merely by flexing and advancing the bronchoscope.

Microbiological samples are easy to obtain from chosen peripheral sites and are of good quality provided adequate precautions are taken to avoid contamination with pharyngeal bacteria.

Biopsies can be taken but because of the size of the biopsy channel (2 mm) the specimens are small and require careful processing.

The rigid bronchoscope is superior for the removal of foreign bodies.

Th.Zimmermann, K.Steen, Department of Pediatrics University of Erlangen-Nurnberg, West-Germany During the pas 25 years, we observed 172 cases of foreign body aspiration i n infants and children.

There was a n increase from 4.6 casesjyear (1962) (1963) (1964) (1965) (1966) (1967) (1968) (1969) (1970) (1971) (1972) (1973) (1974) (1975) (1976) (1977) (1978) (1979) (1980) to 12.1 casesjyear . We found more children younger than 1 2 months in the period from 1981-1986 (11$), compared to 3.4% in the years before and less children younger than 24 months during the same periods (57.65 compared to 73.5%). There were more boys (67%) than girls suffering from a foreign body aspiration. From 1981 to 1906 in 58.8% of all cases, we found different nuts in the bronchial system compared to 75% from 1986 to 1900. There was a n periodic increase of the foreign body aspiration during februaryapril and October to december. Most of the foreign bodys were found i n the bronchial system of the right lung. Until 1900, i n 4.6% more than one bronchoscopy was necessary to remove the foreign body, compared to 1.2% between 1981 and 1986. In 75% of all cases, the children were sent to the hospital with the correct diagnosis. Characteristic signs of the chest were seen in 99% by X-ray diagnostic. During and after the extraction of the foreign body, pnemonia, fever, bronchitis etc. occured i n 27$, when cefotaxim and methylprednisolone was given some hours until one day before, the rate of such complications could be reduced to 8%. In most of the foreign body was removed from the bronchial system 30 minutes after the anaesthesia was started. T h e technique of the foreign body extraction and the evaluation of different parameters from the blood will be discussed. Pediatric Clinic, Rome University "La Sapienza," Italy.

EC and EC % have been shown t o be significantly increased in adult smoking subjects independently of atopy. EC have also been found to be negatively correlated with lung function tests in adults. Passive smoking in children as assessed by the number of cigarettes smoked by parents has been shown to be negatively correlated with lung function and gTowth. No study has addressed the issue of the possible correlation of passive smoking and EC in children.

As a part of a cross-sectional study on determinants of respiratory function and diseases in children this relationship was studied in 159 boys and girls aged 9 yrs: EC were estimated by a culter counter. A s a part of standardized questionnaire on respiratory health, the total number of cigarettes smoked by both parents was estimated and added. It was concluded that EC and EC% are significantly correlated with the total numbers of cigarettes smoked by parents and suggested that this can be an important pathway in the previously described effects of passive smoking upon lung function in children. Seven asthmatic and 12 elite children swimmers without bronchial asthma, swam intervals at a speed 5% below, at the calculated aerobic capacity, and 5% above. Bronchial reactivity was measured by PC-20 histamine 15 minutes before and 15 minutes after the swimming exercises. Lung function, blood gases and blood lactate were measured before swimming, in each interval during swimming and afterwards. Heart rate was recorded electronically during the entire exercise period. Maximal 00, was measured by the Douglas bag method on swimming in a counter-current swim-mill with variable speed of the water flow. PC-20 ranged from 0.145 to 32 mg/ml. Bronchial reactivity increased from before to after swimming ( Variations of bronchial permeability and reactivity related to growth of children can only be measured with follow-up studies: the latter are difficult to perform and data from literature are scanty. Epidemiologic evidence suggests that in children bronchial reactivity decreases with age and that factors like passive smoking can impair lung growth. In order to contribute to this field, 7 5 non-asthmatic children, of the initial age of 11 years ( 4 0 females, 35 males) randomly chosen from a school population of Bologna (Italy) performed annually for three consecutive years a spirometric evaluation before and after an exercise test (free maximal running for 6 minutes). Results showed that: 1) the three years according to predicted values: however, children with passive smoking (one or both parents smoking more than 10 cigarettes per day) showed smaller increase when compared with children of non-smoking parents. The difference was statistically significant for PEF (~(0.01) and FEF 25-75 (p<O.OOl). To study whether bronchial reactivity to exercise is dependent on baseline lung function, 84 asthmatic children aged 7-16 years were investigated. The per centage fall in PEF values after a standard exercise running test was 9.4 2 8.6% in those 39 children with an attack rate of less than 10 per year and 29.6 2 23.3% in those 45 children with an attack rate of 10 or more per year (pC 0.001). A significant negative correlation (r= -0.46, p(O.001) was found between pre-exercise MMEF as well as between other sensitive and reproducible tests of airway calibre and the response to exercise. Such a correlation was not found between the baseline PEF or SGaw values and the exercise response (r=-O.l6 and -0.20, respectively, p>0.05). These results show t h a t bronchial hyperreactivity to exercise is dependent on the residual airway obstruction, but a wide variety of reactivity can occur.

If baseline flow-values less than three standard deviations below predicted are found, however, a clinically significant response to exercise is predicted. We have studied pulmonary function tests in five groups of children from different cities with known high pollution levels of sulphur dioxide and soot. Vital capacity (VC) and forced expiratory volume in one second (FEVl), at repeat measurements (by Electronic Pneumoscreen, Jager), were found to be 20-30% lower than normal in approximately 19-47% of the exposed children. The disturbed function of ventilation (decreased VC and FEV1) was caused by the irritant effect of air pollution. Bronchospasm was not registered in any of the groups, not even after exercise testing. According to illness history, these children had problems with respiratory illness more often than children from a control group living in areas without air pollution. The control group of children had VC and FEVl values normal or above normal. By statistical analys i s of VC in the control group and the group of children from air polluted areas, a significantly high difference was obtained (t=22,53;p<O,Gl). The children from high polluted areas were sent on a two-week recreative stay to a mountain climate free of air pollution. Lung function disorders of these children were reversed VC and FEY1 values, returning to normal, as statistically confirmed, after a two week stay at the mountain (these values were assessed on arrival, after 7 and 1 4 days of stay). Having compared VC of children from Belgrade (B), Gbrenovac (Gb) and Veliki Crljeni (V.Crlj.1, before and after climatic treatment marked differences were obtained: B(before)-B(after): t=10,95;p<G,Gl. Ob(before1-Ob(after): t=12,84;pt0,01. V.Crlj.(before)-V.Crlj.(after):

t=13,46; P<O, 01.

De B l a s i i s MD.R.Ronchetti MD.Pediatric Clinic,Rome Univ

There is convincing e~i d e n c e~~,~~ that SARs are responsible for the classical Hering-Breuer inflation reflex (i.e., the termination of inspiration and prolongation of expiratory time on lung inflation) which, in anesthetized animals, provides the predominant mechanism for regulating the depth and rate of breathing. In fact the activity of SARs related to lung volume, together with the output from bulbopontine neurons, determines the duration of the respiratory cycle and the tidal volume of anesthetized animals.84 A volume threshold, which depends on a given SAR activity, must be achieved to terminate inspiration, and the magnitude of this threshold decreases with time from the onset of inspiration, i.e., larger volumes are needed to switch off inspiration at shorter inspiratory durations. In the absence of volume feedback inspiratory duration is determined only by the bulbopontine mechanism. Expiratory duration is dependent on the duration of the preceding inspiration. The inverse relationship between cycle duration and tidal volume results in an increase in both the rate and depth of respiration when the drive to breathe increases. Without vagal afferents, only the tidal volume will increase in most hyperventilatory circumstances. However, this model does not satisfactorily explain the experimental observations in humanss5 or conscious animals.s6-sa The observation of a reduced vagal feedback in the newborn42.49.52.53 appear to be at odds with the commonly held view that the Hering-Breuer reflex is stronger in the n e w b~r n .~~~~~ This conclusion is based primarily on the presence of inflation apnea in the sleeping newborn and the lack of Hering-Breuer reflexes in conscious a d u l t~.~~-~~ To be consistent with the hypothesis of a stronger Hering-Breuer reflex, the newborn should have an increased sensitivity of the "respiratory centers" to volume-related feedback resulting in a greater reflex effect even if afferent input is reduced compared with the adult. This might reflect an absence of welldeveloped higher influences that in the adult might inhibit the effect of volume feedback.85 On the other hand, as Cross et al.91 pointed out, differences in mechanical properties of the lung might be responsible for the apparent differences in reflex behavior. Indeed, recent comparisons of apnea in newborns and adults of several species following lung inflation and tilting, based on the same Pt, s t i m u l u~,~~~~~ would suggest weaker volume-related vagal reflexes. Moreover, when assessing the importance of the Hering-Breuer mechanism in the newborn, particular attention should be paid to the potential influence of afferents from the rib cage, which undergoes far greater distortion than in the Indeed, during distortion, rib cage afferents are known to provide an additional offswitch r n e c h a n i~m . '~~, '~~ SARs also play a role in the reflex regulation of smooth muscle tone and, in the adult, an increase in SAR activity leads to a reduction in the efferent vagal excitatory activity to airway smooth muscle.'05 This results in a negative feedback mechanism, which, it has been proposed, may serve to optimize the reciprocal relationship between dead space and airway resi~tance.''~ There is no information concerning this in the newborn except for the observations that the neuromuscular mechanism activating tracheobronchial smooth muscle is weaker in the new-born77 and that smooth muscle contraction may excite SARS."~ The observation that RAR activity increases as lung compliance is reduced, together with the fact that they function to promote inspiration, lob supports the hypothesis that RARs are important in the generation of augmented breaths or sighs.Io7 Indeed, in premature infants the ability to provoke an augmented breath is inversely related to dynamic compliance. Furthermore the increase in compliance that occurs with is accompanied by a decrease in the frequency of sighing ( figure 15) .110,111 Once again we are faced with an apparent discrepancy between the above observations and the scant RAR . .Allergy Research Foundation, Inc., Los Angeles, U.S.A. We conducted a randomized c o n t r o l t r i a l of a c u r r iculum, ACT. Seventy-six c h i l d r e n between t h e ages of 8 and 12, whose asthma r e q u i r e d treatment with medications a t l e a s t 2 5 % of t h e days p e r month, were randomized t o c o n t r o l and experimental groups. Over the l a s t 13 months 82 respiratory endoscopies were performed i n children, aged 6 week t o 12 years, admitted w i t h radiological and/or c l i n i c a l evidence of a respiratory infection, preferably before treatment was i n s t i t u t e d . Bronchoscopy,including simple bronchial aspiration (BA) and bronchoalveolar lavage ( B A L ) , was performed on these p a t i e n t s . The BA and BAL were sub- In t h e opinion of the authors t h e indication of therapeutic bronchoscopy i s removing the aspirated respiratory foreign body, aspirating perforated caseous tuberculous lymph node material, excising an intrabronchial turnour or granulation t i s s u e and removing a f i b r o p l a s t i c bronchial secretion.The bronchoscopy was performed under general anesthesia with Storz Hopkins instruments.In the period 1972-1986 they removed aspirated foreign bodies from the trachea-bronchial t r e e of 40 children (27 boys, 13 g i r l s ) . The youngest was 6 months old, t h e oldest 13 years old. The d i s t r ibution by location was: 2 i n t h e trachea, 2 2 on the r i g h t s i d e and 16 on the l e f t s i d e of the bronchial t r e e . The type of foreign bodies was food i n 32 children, namely of vegetal origin (sunflower and other seeds) i n 23 cases, and of animal o r i g i n (bone, meat e t c . ) i n 9 cases. Foreign bodies of non vegetal o r i g i n could be found only i n 8 children.Between 1972-1986 they aspirated t h e perforated caseous material from the bronchi of 9 tuberculous c h i l d r e n (4 boys and 5 g i r l s ) treated with Isoniazid.Tumour-like endobronchial granulation t i s s u e was excised i n 1 case and f i b r o p l a s t i c bronchial secretion was removed from 2 children. Table I gives a survey o f t h e incidence o f r e g u l a r smoking according t o age, class, sex and type o f school.