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cause abdominal discomfort but most patients areunaware of the adult worms in their small intestines.

Nevertheless, ,there may be considerable morbidityduring the early stage of the life cycle when thedeveloping larvae migrate through the liver and lungsbefore returning to the intestine. During this stagethe larvae can cause Loeffler’s syndrome, with

eosinophilia and pulmonary lesions. This

complication has been described from Saudia Arabia,where it is known as seasonal pneumonitis.4 Asthmacan occur at all stages of the infection and may evenresult from exposure to dead Ascaris. This allergicreaction was at one time sufficiently frequent in

laboratory technicians to prohibit the use of Ascarisfor demonstration purposes in academic institutions.There have been very few studies on the importance ofimmune responses in man in endemic areas (far moreis known about ascariasis in pigs).

Theoretically, there should be no difficulty in

controlling ascariasis in the community. There areexcellent drugs such as pyrantel pamoate andalbendazole for treating individual patients and formass chemotherapy and, if they are combined withhealth education and improved sanitation, infectionrates can be greatly reduced. But in the worst affectedareas cultural practices, inadequate financial

resources, and the enormous biotic potential of theworms prevent any serious attempt at control.

Nothing will be achieved unless the communitysanctions the changes in human behaviour that areessential for interrupting transmission and

participates in their implementation. Some degree ofcontrol used to be achieved by the imposition ofcertain measures by dictatorial health officials, but thisapproach is no longer acceptable. However, there areso many other problems deserving immediateattention that ascariasis control will remain a low

priority, not only because health budgets in some areasare so limited but also because public health researchworkers have failed to demonstrate the magnitude ofascariasis as a disease as distinct from Ascaris as aninfection.

All animal species are infected with worms and intheir co-evolution they have established a balance thatbenefits both parasite and host. Man and his domesticanimals are in this respect unbalanced because of theenormous population explosion brought about bysettled agriculture and urbanisation. Simultaneously,there has been a population explosion of parasites and,since the severity of disease caused by worms is usuallyproportional to the number of worms per person,there is undoubtedly a need to reduce the heavy wormburdens, especially in children. Before mass controlcampaigns are advocated in the developing world it isimportant to determine whether the worms confersome as yet unidentified benefits. Perhaps Ascaris andmany other parasites help to protect those who are

4 Gelpi AP, Mustapha A Seasonal pneumonitis with eosinophilia a study of larvalascariasis in Saudi Arabia Am J Trop Med Hyg 1967; 16: 646-57.

infected from more serious parasites and from some ofthe ills that affect more affluent societies.5 Nematodesare potent stimuli for mast cells and mast cell densitiesin "wormy" people are enormously increased. Doesthis observation help to explain the absence of

coronary disease in some poorer countries?

COSINES AND SINUS ARRHYTHMIA

IN healthy people the heart rate varies with the phase ofrespiration, accelerating during inspiration and slowing inexpiration-sinus arrhythmia. The vagus nerve is theefferent pathway7 of the reflex loop producing this rhythmand sinus arrhythmia is abolished by conditions such asautonomic neuropathy that disrupt vagal function. How canone quantify this oscillating rhythm? Two types of analysishave been used-basic bedside tests and computer-basedmethods. Comparison of the heart rate at end-expirationand end-inspiration is readily achieved,B,9 and the range ofnormality has been defined; this analysis is reasonablysensitive and specific for detection of vagal damage inautonomic neuropathy.B,9 However, such bedsidemeasurements sample the heart rate only at the extremes ofthe respiratory cycle.

Mathematical techniques can be used to describe thedistribution of all the heart beats occurring over manyrespiratory cycles; differential equations relating changes inheart rate and thoracic dimension," measurement of thestandard deviation of cardiac cycle length,12 and assessmentof beat-to-beat variability on 24-hour electrocardiograms13are examples of this approach. Another method is based onthe technique of cosinor analysis first described by Halberget al in 1972.14,15 A 3-min electrocardiographic recording iscorrelated with respiration,16 and computer techniques areused to plot the length of each cardiac cycle (in this case thePP interval) against its position in the respiratory cycle. Thedistribution so obtained resembles a sine wave, with the

peak of the curve (the longest PP intervals) at end-expirationand the nadir at end-inspiration. A best fit curve is found bymultiple regression analysis and several variables can becalculated-amplitude of sinus arrhythmia (maximumdeviation of the PP interval from the mean), precise times inthe respiratory cycle of maximum and minimum heart rate,

5. Nelson GS. Parasitic zoonoses. In: England PT, Sher A, eds. The biology ofparasitism. New York: Alan R. Liss, 1988: 13-41.

6. Fernex M, Sternby NH. Mast cells and coronary heart disease: relationships betweennumbers of mast cells in the myocardium, severity of coronary atherosclerosis andmyocardial infarction in an autopsy series of 672 cases. Acta Path Microbiol Scand1964; 62: 525.

7. Samaan A. The antagonistic cardiac nerves and heart rare. J Physiol 1935; 83: 332-40.8. Sundkvist G, Almer L-O, Lilja B Respiratory influence on heart rate in diabetes

mellitus. Br Med J 1979; i: 924-25.9. Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy

Br Med J 1982; 285: 916-18.10. Smith SA. Reduced sinus arrhythmia in diabetic autonomic neuropathy: diagnostic

value of an age-related normal range. Br Med J 1982; 285: 1599-601.11. Clynes M. Computer analysis of reflex control and organization: respiratory sinus

arrhythmia. Science 1960; 131: 300-02.12. Coker R, Koziell A, Oliver C, Smith SE. Does the sympathetic nervous system

influence sinus arrhythmia in man? Evidence from combined autonomic blockadeJ Physiol 1984; 356: 459-64.

13. Ewing DJ, Neilson JMM, Travis P. New method for assessing cardiac

parasympathetic activity using 24 hour electrocardiograms Br Heart J 1984; 52:396-402.

14. Halberg F, Johnson EA, Nelson W, Runge W, Sothern R Autorhythmometry-procedures for physiologic self-measurements and their analysis. PhysiologyTeacher 1972; 1: 1-11.

15. Hrushesky WJM, Fader D, Schmitt O, Gilbertsen V. The respiratory sinus

arrhythmia. a measure of cardiac age. Science 1984, 224: 1001-04.16. Rawles JM, Pai GR, Reid SR. A method of quantifying sinus arrhythmia: parallel

effect of respiration on P-P and P-R intervals. Clin Sci 1989, 76: 103-08.

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and the respiratory contribution to the variation in heartrate. What has cosinor analysis taught us? It has confirmedprevious observations that the amplitude of sinus

arrhythmia declines with age,1O,17 and has shown that the PRinterval tends to alter with respiration in phase with the PPinterval. In a few patients in atrial fibrillation the ventricularresponse is not totally random but is under phasicrespiratory control, although paradoxically the heart ratetends to accelerate rather then decelerate in expiration.18

INHALED STEROIDS AND RECURRENTWHEEZE AFTER BRONCHIOLITIS

1-2% of children are admitted to hospital with acute viralbronchiolitis in the first year of life.’ Three-quarters of theseinfants have recurrent episodes of wheeze and cough in the 2years after admission .2 In some children the symptomsfollowing bronchiolitis may cause no distress and notreatment is needed, but in others recurrent episodes ofdistressing cough, wheeze, and dyspnoea lead to repeatedhospital admissions.2,3 Management of these patients isdifficult. &bgr;2-agonists such as salbutamol or terbutaline areseldom helpful in children younger than 18 months.3,4 Insome wheezy infants, nebulised salbutamol causes

deterioration in lung function,4,5 although the mechanismsfor this paradoxical action remain unclear. Whilst theanticholinergic bronchodilator ipratropium bromide

improves lung function in 40% of wheezy infants aged lessthan 18 months this physiological response is not

necessarily paralleled by clinical improvement.7The possible benefits of inhaled steroids in the treatment

of wheeze following bronchiolitis have lately been studied.Carlsen et al8 treated 22 children (mean age 14 months), whohad had at least one episode of bronchopulmonaryobstruction after acute bronchiolitis, with nebulisedbeclomethasone dipropionate (200-400 µg/day) for 8 weeks.These children had fewer episodes of wheezy breathlessnessand received less bronchodilator treatment than children ina carefully matched control group receiving placebo.Surprisingly, the benefit from beclomethasone dipropionate(BDP) persisted for several weeks beyond the treatmentperiod, suggesting a prolonged effect on bronchial

hyperreactivity. Maayan et al9 showed a significant

17. O’Brien IAD, O’Hare P, Corrall RJM. Heart rate variability in healthy subjects: effectof age and the derivation of normal ranges for tests of autonomic function. Br HeartJ 1986; 55: 348-54.

18. Rawles JM, Pai GR, Reid SR. Paradoxical effect of respiration on ventricular rate inatrial fibrillation. Clin Sci 1989; 76: 109-12.

1. Phelan PD, Landau LI, Olinsky A. Respiratory illness in childhood. Oxford:

Blackwell, 1982: 76-84.2. Henry RL, Hodges IGC, Milner AD, Stokes GM. Respiratory problems 2 years after

acute bronchiolitis in infancy. Arch Dis Child 1983; 58: 713-16.3. Milner AD, Murray M. Acute bronchiolins in infancy: treatment and prognosis.

Thorax 1989; 44: 1-5.4. Prendiville A, Green S, Silverman M. Paradoxical response to nebulised salbutamol in

wheezy infants, assessed by partial expiratory flow-volume curves. Thorax 1987;42: 86-91.

5 O’Callaghan C, Milner AD, Swarbrick A. Paradoxical deterioration in lung functionafter nebulised salbutamol in wheezy infants. Lancet 1986; ii: 1424-25.

6. Hodges IGC, Groggins RC, Milner AD, Stokes GM. Bronchodilator effect of inhaledipratropium bromide in wheezy toddlers. Arch Dis Child 1981; 56: 729-32.

7. Henry RL, Milner AD, Stokes GM. Ineffectiveness of ipratropium bromide in acutebronchiolitis. Arch Dis Child 1983; 58: 925-26.

8. Carlsen KH, Leegard J, Larsen S, Orstavik I. Nebulised beclomethasonedipropionate in recurrent obstructive episodes after acute bronchiolitis. Arch DisChild 1988; 63: 1428-33.

9 Maayan C, Itzhaki T, Bar-Yishay E, et al. The functional response of infants withpersistent wheezing to nebulised beclomethasone dipropionate. Pediatr Pulmonol1986; 2: 9-14.

improvement in specific airway conductance (a measure ofairflow limitation), tachypnoea, chest retraction, and

wheezing after 2 weeks’ treatment with nebulised BDP (300µg/day) in 9 infants aged less than 9 months with frequentwheeze and dyspnoea following bronchiolitis, but thisbenefit disappeared rapidly after stopping BDP. There havebeen anecdotal reports of symptomatic improvement inwheezy infants treated with another inhaled steroid,budesonide, delivered either from a pressurised aerosol intoa large spacer device (’Nebuhaler’) or via a nebuliser.10,11These reports suggest that inhaled steroids may help a groupof children who have previously been difficult to treat.However, the results raise several important issues that needto be resolved before routine use of inhaled steroids in suchchildren can be advocated.

In controlled clinical studies of preschool children withasthma, nebulised BDP was of little12 or no13 benefit. Fromthese studies and clinical experience, it appears thatnebulised BDP is less effective than BDP delivered from a

dry-powder or pressurised metered-dose inhaler; it isunclear whether properties of the suspension or difficultiesin delivering an adequate dose of the active drug to the lungaccount for the differences in response. By contrast,budesonide delivered via a nebuhaler is an effective

prophylactic treatment for preschool children with frequentepisodes of asthma. 14The sustained improvement after completing the course

of BDP seen in Carlsen’s patients8 is remarkable. Althoughthe mechanisms of action of inhaled steroids in bronchial

hyperreactivity are complex and not fully understood,ls inolder children and adults with asthma the suspension oftreatment with inhaled steroids is usually associated withworsening of symptoms within days. Carlsen’s results, ifconfirmed, would suggest that the bronchial hyperreactivitythat follows bronchiolitis differs from that in asthma, if onlyin the duration of the response to inhaled steroids. However,lung function in Maayan’s patients deteriorated rapidly tothe pretreatment level on stopping BDP therapy.

Differences in dose, duration of treatment, andsimultaneous use of other drugs make comparisons of thedifferent reports of nebulised BDP difficult. The daily dosevaried from 200 Ilg to 1200 µg.8,16 Higher doses of inhaledsteroids may retard growth.17 Small differences in studydesign and in the way the drug is nebulised and deliveredmay explain some of the conflicting results.1B Differentclinical definitions of bronchiolitis were used to select

subjects and virus isolation was not a prerequisite ofinclusion in any of the studies. Moreover, it is not alwaysclear whether the symptoms described followedbronchiolitis or were manifestations of asthma. The low

frequency of atopic disease in children who have had

10. McCarthy TP. Nebulised budesonide in severe childhood asthma. Lancet 1989; i:379-80.

11. Godfrey S, Avital A, Rosler A, Mandelberg A, Uwyyed K. Nebulised budesonide insevere infantile asthma. Lancet 1987; ii: 851-52.

12. Storr J, Lenney CA, Lenney W. Nebulised beclomethasone dipropionate in preschoolasthma. Arch Dis Chil 1986; 61: 270-73.

13. Webb MSC, Milner AD, Hiller EJ, Henry RL Nebulised beclomethasone

dipropionate suspension. Arch Dis Child 1986; 61: 1108-1014. Gleeson JGA, Price JF. Controlled trial of budesonide given by the Nebuhaler in

preschool children with asthma. Br Med J 1988; 297: 163-66.15. Moms HG. Mechanisms of action and therapeutic role of corticosteroids in asthma.

J Allergy Clin Immunol 1985; 75: 1-13.16. Pedersen W, Prahl P. Jet-nebulised beclomethasone dipropionate in the management

of bronchial asthma. Allergy 1987; 42: 272-75.17. Littlewood JM, Johnson AW, Edwards PA, Littlewood AE. Growth retardation in

asthmatic children treated with inhaled beclomethasone dipropionate Lancet 1988,i: 115-16.

18. Clarke SW. Commentary. Arch Dis Child 1986; 61: 1110.