Thorax 1996;51:59-63

Usual dietary salt intake and asthma inchildren: a case-control study

Kitaw Demissie, Pierre Ernst, Katherine Gray Donald, Lawrence Joseph

AbstractBackground - A decline in host resistancedue to an alteration in diet - primarily ofsalt -was recently put forward as a possibleexplanation for rising rates of asthma.Methods - A case-control study was co-ducted in participants in a prevalence sur-vey which included 187 children withasthma (defined by prior diagnosis and/ora decline in forced expiratory volume inone second (FEVy) of > 10% after exercise)and 145 age and sex matched controls.Subjects were selected from 989 childrenaged 5-13 years attending 18 elementaryschools on the island of Montreal. Usualdietary salt intake was estimated froma food frequency questionnaire ad-ministered to the mother, and a salt intakescore was used to group the children intoquartiles from I (lowest) to IV (highest saltintake). Bronchial hyperresponsiveness tomethacholine was assessed by Yan'smethod. Cases and controls were com-bined in one group to examine therelationship of salt intake to bronchialhyperresponsiveness to methacholine.Methacholine responsiveness was ex-pressed as a dose-response slope and ranksof dose-response slopes were used in theanalysis.Results - After accounting for importantconfounding variables, there was no as-sociation between asthma and salt intake,while methacholine dose-response sloperanks increased with increasing salt intakeand methacholine responsiveness wasgreater in the highest quartile than in thelowest quartile of salt intake. The mediandose-response slopes in % fall in FEVy per1tmol methacholine for quartiles I, II, III,and IV were 5 4, 5.9, 7.7, and 8-7.Conclusions - No association was foundbetween asthma or exercise-inducedbronchospasm and dietary salt intake.Bronchial hyperresponsiveness to metha-choline did, however, appear to in-crease with greater salt intake, but therelevance of this association to asthma isunclear.(Thorax 1996;51:59-63)

Keywords: salt intake, bronchial hyperresponsiveness,children.

Asthma morbidity and mortality is greater incommunities adopting a more western lifestyle

and in migrants as they move from ruralunderdeveloped to urban westernised areas.1`4The lack of an adequate epidemiological ex-planation for this phenomenon, coupled withthe increase in salt consumption withurbanisation, led Burney2 to hypothesise thatincreased sodium intake might be partlyresponsible for the increased mortality andmorbidity due to asthma. He tested the hypo-thesis using regional data from England andWales and found a strong correlation betweentable salt purchases and asthma mortality inmen and children of both sexes, but not inwomen. Two controlled crossover trials56 haverecently found increasing dietary salt intake toresult in worsening asthma symptoms and anincrease in bronchodilator consumption. Thedegree to which such salt loading might beapplicable to salt consumption observed in un-controlled situations is unclear.

In contrast, Lieberman and Heimer7 in anon-blinded randomised crossover trial in-volving 17 asthmatic patients found no sig-nificant difference in peak flows or peak flowvariability between periods of low and high saltintake. Pistelli et al conducted a communitybased cross sectional study in children aged9-16 years and found the reported use of tablesalt to be strongly related to respiratory symp-toms suggestive of asthma in boys, but not ingirls. These discrepancies in the reported res-ults of the different investigations and the lim-ited data arising from community based studiesof children9 led us to examine the relationship ofnormal dietary salt intake to asthma in children.

MethodsA case-control study among participants in across sectional survey was conducted in thecity of Montreal, Canada from April 1990 toNovember 1992. Eighteen schools were se-lected on the island of Montreal in order torepresent a broad range of socioeconomic sta-tus. One class from each school from each ofgrades 1 (age 5-7 years), 3 (age 8 and 9 years),and 5 (age 10-13 years) was selected. A ques-tionnaire on history of asthma diagnosed bya doctor, respiratory symptoms and illnesses,asthma in a parent, exposure to second-handtobacco smoke, housing conditions includingthe current presence of pets, and a letter ofconsent were completed by parents.

In the school gymnasium each subject's age,sex, height, and weight were recorded andspirometric tests were carried out sitting andwith nose clips using two Collins 10 litre water-

RespiratoryEpidemiology UnitK DemissieP Ernst

Department ofEpidemiology andBiostatisticsL Joseph

McGill University,Montreal, Quebec,Canada

School of Dieteticsand Human Nutrition,Macdonald Campus ofMcGill University,Montreal, Quebec,CanadaK G Donald

Correspondence to:Dr P Ernst, RespiratoryEpidemiology Unit, McGillUniversity, 1110 Pine AveWest, Montreal, Quebec,Canada H3A 1A3.Received 12 April 1994Returned to authors18 July 1994Revised version received6 October 1994Accepted for publication7 September 1995

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sealed spirometers (Warren E Collins, Brain-tree, Massachusetts, USA) according to currentAmerican Thoracic Society guidelines,'0 andthe best FEV, from any flow-volume curve,both at baseline and after exercise, was used foranalysis." Following five minutes of inactivity,heart rate was measured using a digital ple-thysmograph (Heart Rate Inc, Costa Mesa,California, USA). Children then ran aroundthe gymnasium for six minutes at a pace judgedsufficient to attain > 90% of the predictedmaximal heart rate'2; heart rate was remeasuredimmediately on completion of exercise. Fiveand 10 minutes after completion of exercisethe spirometric tests were repeated on the samespirometer. Average room temperature and rel-ative humidity, as well as percentage maximumheart rate attained, were similar among childrenwho did and did not demonstrate a > 10%fall in FEVy after exercise (exercise-inducedbronchospasm). Subjects did not take part inthe exercise test if they were excused from gymclass or if their FEVy was below 70% predicted.No specific instructions were given concerningthe use of medications including those forasthma. The exercise test was completed suc-cessfully in 989 children. Only 11 (1 11%) hadbeen dispensed a bronchodilator (for example,3 agonist) at the time of the test.The subjects for the case-control study were

selected from the participants in the cross sec-tional survey. A case was defined by the pres-ence ofeither (1) a history ofasthma as reportedby parents, or (2) a fall in FEV1 of ) 10% afterexercise. ' The next child on the alphabeticalclass list ofthe same sex as the case, but withouteither of these criteria for asthma, was chosenas a control. If the parents of the case refusedfurther participation, both this child and theone chosen to serve as a control were notstudied further, while if a child chosen as acontrol (that is, without asthma or exercise-induced bronchospasm) refused, the nextappropriate child on the class list was selected.For 38 cases a comparison child could not beobtained.A food frequency questionnaire designed

specifically to assess the normal intake of saltin the diet of the child was administered to aparent (almost always the mother). Food itemshigh in sodium'4 that are frequently consumedwere grouped into nine food groupings; portionsizes were not indicated. Parents were alsoasked about their child's preference for saltyfoods. Parents chose from four frequency cat-egories for each of the nine food groups theirchild might consume, and a score was obtainedfrom the sum of the items multiplied by thefrequency of each item (maximum value 27).The salt preference score obtained by askingthe question: "Does your child like saltyfoods?" (very much, 2; somewhat, 1; not at all,0) was then added to obtain the overall saltintake score (maximum value 29). The ques-tionnaire is provided in the appendix. Foodfrequency is widely used as the dietary methodof choice to provide an approximate rankingof the normal intake of individuals on a specificdietary component.'5 In measuring salt intake,such an estimate of usual intake is particularly

important because of the high day-to-day vari-ability in intake.'6The last occupation of the parents was trans-

formed into the corresponding codes of theCanadian Classification and Dictionary of Oc-cupations.'7 These codes were then convertedinto socioeconomic status scores for the childbased on income and education level for eachoccupation from the tables developed byBlishen and colleagues.'8 The highest scorefrom either parent was retained for analysis.

In order to investigate in detail the risk factorsfor bronchial hyperresponsiveness, metha-choline bronchoprovocation and allergy skintests were performed on cases and controls athome in the evening. All children with an FEV1of >75% of their forced vital capacity had amethacholine challenge test using the methodofYan.'9 A long protocol with nine incrementaldoses was followed among the cases, with sixincremental doses given to the controls. Thetest began with three inhalations of 0 9% salinewith FEV, being measured one minute later.Provided that the FEV, did not fall by morethan 10% of the baseline value, methacholinesolutions were administered according to thefollowing cumulative doses in ,tmol: 0 030,0-060, 0 124, 0-244, 0 499, 0-996, 1 990,3'913, and 7-80 for the long protocol and0 030, 0 094, 0.477, 1-967, 3-89, and 7-78 forthe short protocol. At each dose level subjectsperformed inspiratory capacity inhalation witha five second breath hold while seated andwearing nose clips. A forced expiratory man-oeuvre was performed 60 seconds after eachdose. The challenge was stopped when theFEV, had fallen by 20% or more, or the finaldose had been reached.

Solutions for allergen skin testing comprisedhistamine (1 mg/ml), normal saline, Dermato-phagoides pteronyssinus, Dermatophagoidesfarinae, mixed grass pollens, tree pollens,ragweed, mixed moulds, Aspergillus sp, cat epi-thelium, and cockroach antigen. Needles (26gauge) were used to break the skin. The res-ultant weal diameters were measured at rightangles using Vernier callipers at 10 and 15minutes. A weal of > 3 mm was taken as apositive response. If there was no positive re-sponse to histamine, skin testing was regardedas invalid.The study was approved by the ethics com-

mittee of McGill University.

DATA ANALYSISThe salt intake score was used to group thechildren into quartiles (quartile I with the low-est and quartile IV with the highest salt score,respectively). The relationship between asthmaand salt intake was examined using a logisticregression model20 before and after adjustingfor potential confounding variables. Statisticalsignificance of the regression coefficients wasdetermined by the X' approximation to thelikelihood ratio statistic.

Cases and controls were combined into onegroup in order to investigate the relationshipof salt intake to bronchial hyperresponsivenessto methacholine. For the methacholine broncho-

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Table 1 Descriptive characteristics of the subsample selected for further study at home

Cases Controls

Participants Non-participants Participants Non-participants(n= 187) (n = 82) (n = 145) (n = 86)

Boys (%) 55-4 53-2 52-5 58-5Caucasians (%) 74-6 86-1 82-0 83-3Mother smokes (%) 37-3 45-2 43-2 46-3Father smokes (%) 43-5 508 505 56-1Smoked while pregnant (%) 29-6 43-1 33-9 32-9History of asthma (%) 44 9 37 2 NA NAOther respiratory history* (%) 47-1 58-9 33-1 41 1

* History of either pneumonia, bronchiolitis, whooping cough, or croup.NA=not applicable.

provocation test the dose-response data ofeach child were summarised according to themethod ofO'Connor et al" - that is, percentagedecline in FEVI/dose - where percentage de-cline in FEV1 was defined as the decline inFEV1 (from the post saline value) after the finalmethacholine dose, and dose was defined as

the final cumulative methacholine dose ad-ministered. This method of expressing metha-choline responsiveness in population studieshas been validated by several groups.2223 Thedose-response slope was ranked because ofthe non-normal distribution which persisted,despite various transformations. The rankswere used as an outcome variable for sub-sequent multivariate linear regression analysiswhere approximate normality was observed inthe residuals.

Statistical analysis was carried out using SASand EGRET statistical softwares.2425

ResultsA total of 1274 children were eligible to par-ticipate in the cross sectional survey from 18Montreal schools selected. Ofthese, the parentsof 130 children (10.2%) refused participationfor their children, while a further 75 children(5 9%) did not return the questionnaire andconsent form. There were no meaningfuldifferences between participants and non-par-ticipants as to the age of the child (mean (SD)8-8 (1-8) versus 8-0 (1-9)), sex (boys: 51%versus 55%), race (Caucasians: 78% versus

81 %), socioeconomic status assessed by neigh-bourhood census data (poorest socioeconomicstatus quartile: 27% versus 23%). Spirometrictests were not performed for a further 23 chil-dren because of illness or absence from school.Of the 1046 children who attempted spiro-metric testing, 28 (2 7%) were unable to com-plete the test successfully and such failure wasmore common among younger children butwas unrelated to reported respiratory illness,symptoms, or socioeconomic status. The spiro-metric data of a further 28 children (2 7%)were lost after the test. One child (0 1%) wasexcluded because of a severe attack of asthmaat the time of the test.Of the 989 children (77 6%) who par-

ticipated in the cross sectional survey and hadspirometric data, 269 children (27 2%) metthe case definition and for 231 of these casesa child of the same sex in the same class was

available to serve as a control. Of the 269

children with either exercise-induced broncho-spasm or a history of asthma (80 of whom hada history of asthma alone), 187 (70%) werevisited at home. Of the 231 children withoutexercise-induced bronchospasm or a history ofasthma, 145 (63%) were visited. Among thecases (table 1), non-participants were morelikely to be Caucasian, have mothers or fatherswho currently smoke, or mothers who hadsmoked during pregnancy. Asthma, but not ahistory of other respiratory illness, was morecommon among participants, indicating an in-creased interest in the study by parents ofchildren with this common childhood disorderdespite the fact that our study was presentedas an inquiry into respiratory health in general.Among the control group differences betweenparticipants and non-participants were less pro-nounced, although they were mostly in a similardirection to the cases.The prevalences of wheeze, allergy skin test

positivity, and bronchial hyperresponsivenessto methacholine were higher among the casesthan the controls, while pre-exercise lung func-tion levels were lower (table 2).

Table 3 presents the relationship of usualdietary salt intake to childhood asthma (definedby a history of asthma and/or a decline in FEV1of > 10% after exercise). Usual dietary saltintake was not found to be associated withasthma in children when examined crudely orafter adjusting for the effects of age, sex, race,asthma in a parent, socioeconomic status, andprenatal and postnatal exposure to tobaccosmoke. The inequality of cells in the quartilesresulted from ties in the values of the salt score.

Table 2 Indicators of asthma among the cases andcontrols

Cases Controls(n= 187) (n= 145)

Ever wheeze (%) 49-2 19 7Allergy skin test positivity (%)** 43-7 31-4Asthma in a parent (%) 18-5 6-0Methacholine responsive (%)t 31-0 19-4FEV,t -1-50 + 1-54FEVI/FVCt -0 40 +0 39

FEV, = forced expiratory volume in one second; FVC= forcedvital capacity.** > 3 mm weal to one or more of the nine aeroallergens tested(see text for explanation).t Children with >20% fall in FEV, after < 7-8 imol metha-choline.t FEV, and FEVI/FVC were expressed as change from 100%in ratio of observed to expected value and are adjusted for sex,race, the natural logarithm (ln) of height, ln of age, and ln ofbody mass index.

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Table 3 Unadjusted and adjusted odds ratios (with 95% confidence intervals) for theassociation of salt intake with asthmatSalt score quartiles* n Unadjusted odds ratio Adjusted odds ratiot

I 76 Reference category Reference categoryII 79 0 90 (0-48 to 1-70) 1-07 (0-51 to 2 27)III 82 0 90 (0-48 to 1-69) 0-81 (0-37 to 1-78)IV 95 0 89 (0 49 to 1-62) 1-12 (0 54 to 2-33)

* Salt intake increases from quartile I to IV (see text for explanation).t Asthma is defined as a >10% decline in FEV, after exercise and/or a history of diagnosedasthma.: Adjusted for age, sex, race, asthma in a parent, socioeconomic status, and prenatal and postnatalexposure to tobacco smoke.

Table 4 Relationship of dietary salt intake tomethacholine dose-response slope (DRS)

Salt score DRS rank coefficient Median DRSquartilest (95% CI)t (% per pmol)

I Reference category 5-4II 5-7 (-24-9 to 36 3) 5-9III 28-4 (-2-8 to 59-7) 7-7IV 34-2 (4-2 to 642) 8-7

95% CI=95% confidence interval.t Salt intake increases from quartile I to IV (see text for ex-planation).i Coefficient is adjusted for age, sex, race, parental asthma,socioeconomic status, and prenatal and postnatal exposure totobacco smoke.

We also investigated the relationship betweenusual dietary salt intake and bronchial hyper-responsiveness to methacholine by combiningboth cases and controls into a single group.Table 4 shows the relationship of methacholinedose response to dietary salt intake afteraccounting for the effects of potential con-founding variables. The ranks for dose-responseslope increase with increasing salt intake andare significantly different between the highestand lowest quartiles. To illustrate this, mediandose-response slopes are calculated within eachquartile of salt intake. There were no significantdifferences in these relationships accordingto sex, allergy skin test positivity, or race(non-significant interaction terms).

DiscussionWe were unable to show any association be-tween usual salt intake and diagnosed asthma orexercise-induced bronchospasm using a case-control design. When considering cases andcontrols as a single group, however, we foundbronchial hyperresponsiveness to methacholineto increase with usual dietary salt intake. Thisdiscrepancy could be due to the different patho-physiological mechanisms underlying exerciseand methacholine airway challenges.26The measure of salt intake used in this study

has not been validated because of the difficultyin collecting multiple 24 hour urine samples ina large number ofchildren. The dietary methodmost appropriate for measuring usual dietaryintake of a single nutrient is a food frequencyquestionnaire. 4 Food frequency questionnairesfor other nutrients have been used widely andfound to relate well to more detailed methodsofdietary evaluation.'4 Misclassification of chil-dren for salt intake is likely, however, and might

have resulted in the attenuation of the as-sociation between salt and asthma among ourstudy subjects.

Since children were more likely to have beenincluded in the subsample studied if they hada history of asthma or demonstrated exercise-induced bronchoconstriction, and becausesuch traits are related to methacholine re-sponsiveness, a spurious correlation betweenmethacholine responsiveness could have beencreated if a history of asthma or exercise-induced bronchospasm were related to saltintake. This was not the case, however. To besure such confounding was not present, therelation between methacholine responsivenessand salt intake was re-examined after adjustingfor the occurrence of exercise-induced bron-chospasm or a history of asthma and the re-lationship was unchanged.The fact that more children of smoking

mothers did not participate in the study couldhave attenuated the association between usualsalt intake and asthma. This is because smokingis more prevalent in mothers with low socio-economic status and it is possible that socio-economic status and salt intake are related."7At the same time, exposure to environmentaltobacco smoke and airways responsiveness maybe related.'8 Thus, non-participation of smok-ing mothers will result in the preferential ex-clusion of children with a high intake of saltand with airways hyperresponsiveness. How-ever, socioeconomic status and usual dietarysalt intake were not found to be related in ourdataset.The biological mechanisms that might ex-

plain the role of dietary salt intake in airwaysresponsiveness remain uncertain. As sum-marised by Burney,' the added dietary sodiumload might increase the contribution of theelectrogenic Na+ pump to the resting mem-brane potential and potentiate the hyper-polarisation of the bronchial muscle cells.A common aetiological role of dietary sodiumto both asthma and hypertension is also sug-gested.' Bronchial hyperresponsiveness hasbeen linked to increased Na+/K+ ATPase ac-tivity in animal models,29-31 as well as to in-creased extracellular K+ and smooth musclecontraction.32-3' The control of potassiumhomeostasis is through the adrenergic systemand this control is impaired in asthmatic sub-jects.35 This might explain the previously re-ported relationship observed between urinarypotassium excretion and bronchial hyper-responsiveness.35

In conclusion, we found dietary salt intaketo be related to bronchial hyperresponsivenessto methacholine, but not to childhood asthma,as determined by a history of asthma and/or adecline in FEV, by > 10% after exercise. Ourresults further underline the conclusions ofprevious studies36 that the study of risk factorsfor asthma in community based studies maybe substantially affected by the measure ofasthma chosen, and that measures of non-specific bronchial responsiveness may be lesshelpful than initially hoped.

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AppendixFOOD FREQUENCY QUESTIONNAIREBelow is a list of foods your child may eat.Please indicate how often your child eats eachof the foods.

Most 3-5 1-2 Less thandays times times once

per week per week per week

Cheese slices

Bacon or salami orbologna, etc

Potato chips, peanuts,pretzels, corn chips,etc

Salted crackers

Canned or packagedsoup

Kraft dinner, lasagna

Frozen TV dinners,pot pies, etc

Dill pickles

Ketchup, soy sauce

Do you like salty foods?

Very much

Somewhat

Not at all

Do you usually add saltto foods?

Yes

No

The authors acknowledge the advice of Professors MargaretBecklake and Ben Armstrong.

This study was supported by the Medical Reseach Councilof Canada and the Respiratory Health Network of Centres ofExcellence (Canada). PE is Senior Chercheur Boursier, Fondsde la Recherche en Sante du Quebec.

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