ORIGINAL

Niger J Paed 2013; 40 (1):50 - 54

Oviawe O

Osarogiagbon OW

Dip patterns in asthmatic and

non-asthmatic children in

Benin-city, Nigeria

Abstract Objective: Although the

calibre of the airway is kept patent

by multifactorial control system,

there is evidence that the calibre of

the bronchi varies with time of the

day in normal subjects. Asthma is

now known to be a chronic inflam-

matory disease and this chronic in-

flammation causes hyperreactivity

and lability in the airway. Therefore,

asthma is characterised as a disease

where respiratory symptoms are

based on large variation in airway

calibre leading to variations in resis-

tance to airflow over a short period

of time.

similar for age, weight and height,

DOI:http://dx.doi.org/10.4314/njp.v40i1,9.

Accepted: 13th July 2012

but the mean daily PEFR was sig-

nificantly lower for the asthmatic

children (P<0.01). The circadian

pattern of distribution of PEFR is

similar both in asthmatic and the

healthy children, the lowest PEFR

was at 6am and maximum was at

2pm and thereafter, there was a

gradual fall from the 6pm to 10pm,

this was the dominant pattern both

in asthmatic and the healthy chil-

dren. Significant difference in mag-

nitude of PEFR between the two

groups occurred at 6am, 6pm and

10pm (P<0.01). In all, the asthmat-

ics had lower value. The PEFR in

each case at 2pm was similar; 302.6

l/min for normal children as against

3.2 l/min for asthmatic children. Of

the asthmatic subject, 205 (97.6%)

had a discernable dip pattern com-

pared with 4 (2.2%) in healthy sub-

jects.

Conclusion: Dip pattern exists both

in asthmatics and non-asthmatic

children, although, more of the

asthmatics had a discernable dip

pattern. The airway calibre shows a

variation with the time of the day,

both in asthmatics and normal sub-

jects with lowest values in the

morning and highest in the after-

noon. But at each time of the day,

the asthmatics had lower PEFR

values than normal children. This

maybe relevant in the management

and follow-up of the asthmatics.

Oviawe O

(

)

Osarogiagbon OW

Department of Child Health

University of Benin Teaching Hospital

Benin City, Nigeria

Email: sonofeto@yahoo.com

Method: Normal non-asthmatic chil-

dren leaving within 10km of Uni-

versity of Benin Teaching Hospital

(

UBTH) and whose parents work at

UBTH were recruited. These sub-

jects aged 5 – 15 years were initially

matched with an index asthmatic

case both for sex and age (within six

months range). Using a question-

naire the control were screened to

exclude any case with history of

respiratory, cardiac or any form of

active disease or chest deformity or

family history of asthma. This was

followed by weight and height de-

termination. Both the subject and

control were then instructed on the

correct use of the mini Wright Peak

Flow meter and how to record it in

the diary provided. After five days

of measurement, the diaries were

collected and the PEFR were ana-

lysed.

Results: Two hundred and ten (210)

asthmatics and one hundred and

eighty healthy children completed

the study. The two groups were

Key words: Asthma, dip pattern,

circadian rhythm, Peak expiratory

flow rate.

1

-3

Introduction

system acting on the bronchial muscles. However,

there is evidence tha_-t₄ the calibre of the bronchi vary

1

Bronchia_,₂l airways remain patent under normal circum-

with time of the day. This circadian rhythm is reported

1

stances. The mechanisms for maintaining this is com-

to be more pronounced in_-₇subjects with asthma than in

5

plex but it is often through a multifactorial control

normal, healthy subjects. The characteristics of this

5

1

rhythm is easily demonstrable by serial measurements of

peak exp_,₇iratory flow rate (PEFR) at different times of

of asthma patients include aged five years up to 15

years, a history of variable wheezy breathlessness and a

demonstration of a more than 20% improvement in

PEFR after inhaled or oral salbutamol or a more than

50% improvement of PEFR over the course of hospital

admission. They were studied during convalescence at

home and recorded their PEFR before taking prescribed

medication (where applicable): 150 patients received

salbutamol as and when necessary (PRN), 49 on con-

tinuous (twice daily) salbutamol while 11 had salbuta-

mol thrice daily. None had corticosteroid during the

study period.

6

the day. Measurements in adults and recently children

reveal₅_,₆s_,₈ignificant fluctuations with characteristic pat-

terns.

The most commonly shown is the phenomenon

of morning dip which im₇p_,₈l_,₉ies significant fall of PEFR

during the morning time. The aim of the study is to

define the possible dip patterns in asthmatic Nigerian

children and relate these to clinical asthma.

Materials and Methods

Normal non-asthmatic children living within 10km ra-

dius of University of Benin Teaching Hospital and

whose mother or father or both work at the University of

Benin Teaching Hospital were recruited for the study.

These subjects, aged five years up to 15 years were ini-

tially matched with an index case both for sex and age

Data Analysis

The PEFR values represent the mean of recordings ob-

tained on the 14 consecutive days. A pattern was ac-

cepted when it occurred in at least 80% of daily re-

cordings and at least a 5% difference between highest

(Acrophase) and lowest (Trough) readings. Daily pat-

terns were defined with reference to the acrophase and

trough time.

(

within 6 months range) of asthma and agreed to record

their own PEFR at home. The list of such subjects were

compiled and participation in the study occurred during

holidays or work stoppages by teachers. Using a ques-

tionnaire, the control subjects were screened to exclude

any cases with history of respiratory, cardiac or any

form of active disease or chest deformity or family his-

tory of allergy or asthma and followed by weight (bath

room scale) and height (stadiometer) determination. The

subjects were further instructed by the researcher and his

trained assistants on the correct use of the min Wright

Peak Flow meter and the recording of the measurement

in a diary provided for that purpose. This initial contact

and teaching took place at the children’s homes and in

the evenings and lasted three to five days. Having ascer-

tained proficiency in use of the meter and PEFR re-

cording, the actual study comprised five (5) daily meas-

urements of the PEFR, in a standing position at 6am,

For statistical analysis, mean and standard deviation

(SD) were determined for parametric observations and

inter group comparison done with the students t-test.

The Chi Square (X test) was used in comparing propor-

tions. The accepted level of statistical significance was P

-value less than 0.05.

2

Results

Two hundred and ten asthmatics and one hundred and

eighty normal healthy children completed the study. As

shown on Table 1, the two groups were similar for age,

weight and height but differed in the mean daily PEFR

with significantly lower value for the asthmatic children

(P<0.01).

1

0am, 2pm, 6pm and 10pm and for fourteen (14) con-

secutive days. Three readings of the PEFR were taken at

each time period to the nearest 0.5 litres with a minute

(

60 seconds) rest between readings. Mothers were fur-

ther instructed to ensure PEFR determination and re-

cording were accomplished not later than 15 minutes of

the stipulated time of recording.

Table 1: Anthropometric Data for Asthmatic and Non-

Thereafter, the homes were visited twice: on the second

day, to detect and correct errors if any and, the 15 day

to retrieve the diary card(s) and the Peak Flow Meter

with plastic mouth piece(s) (multiple participation in

some households).

Asthmatic Children

th

Characteristic

Asthma

9.6

Non-Asthma

9.6

Mean Age (years)

Range

5 – 15

5.3 – 15.0

82/98

Two hundred and ten normal healthy children were ini-

tially recruited of which 30 were excluded from the

study: 11 subjects for evidence of falsification of PEFR

readings, 19 for irregular and incomplete recordings,

lasting less than 10 days, and four for hitherto undiscov-

ered positive asthma history in grandparents.

Sex (M/F)

115/95

Weight (Mean ± SD) kg

27.2 ± 6.3

28.4 ± 7.9

Height (Mean ± SD) cm

PEFR (Mean ± SD) L/min

134.6 ± 12.3

276.21 ± 41.7

132.7 ± 11.9

288.14 ± 5.2*

Using a similar protocol of PEFR measurement to that

described for normal healthy children, the study was

carried out in 210 asthma children: criteria for selection

* The difference is statistically significant; p<0.01

5

2

Figure 1 demonstrates the circadian distribution of

PEFR in healthy and asthmatic children. The patterns

are similar, with a gradual rise of PEFR from 6am up to

maximum values at 2pm and thereafter, a gradual fall in

the PEFR through 6pm to 10pm. Significant differences

in magnitude of PEFR in the two groups occurred at

6

am (P<0.001); 6pm (P<0.01) and at 10pm (P<0.01)

with the asthmatic recording lower values. The PEFR

values in each case at 2pm was similar; 302.6 for normal

children as against 297.2 for asthmatic children. The

acrophase tome was 2pm in 150 (71.4%) while trough

times was 6pm in 161 (76.7%) asthma cases. None of

the asthmatic had trough values at 2pm and none had

acrophase PEFR at 6am.

Fig 2b: Dip patterns in asthmatic children showing morning

dip

Of the asthmatic subjects, 205 (97.6%) had discernable

dip patterns and this compares with 4 (2.2%) cases in

healthy subjects.

Fig 2c: Double dip patterns in asthmatic children

Figure 3 shows the relationship between times of onset

of asthma all attacks or most of the attacks and dip pat-

terns. Of 122 asthma cases with onset of asthma attack

in the morning, 102 (83.6%) had morning dip. On the

other hand, only seven cases (9%) of those with onset of

asthma attack in the evening had morning dip. Further-

more, onset of asthma attack in the afternoon was less

common (4 cases) and none had morning or evening dip.

Majority of the asthmatic children (61.5%) with onset of

attack in the evening had evening dip followed by dou-

ble dip”. Also from the same figure 3, majority of those

with attack in the morning were also morning dippers.

Dip patterns correlated significantly with time of onset

Fig 1: Distribution of PEFR at various times of day in normal

and asthmatic children

Figure 2 (a – c) demonstrates the various dip patterns in

asthmatic children: Evening dip (2a); Morning dip (2b);

Double dip and No dip (2c). The most common pattern

was morning dip and occurred in 110 (52.4%) asthma

cases; followed by double dip (31%) and evening dip

(

14.2%) cases. Of the 4 healthy children with dip pat-

2

terns, 3 had morning dip while the remaining case had

evening dip. These dip patterns were however shallow

when compared with those in asthmatic children.

of asthma attack (X = 104.4; P<0.00001).

Fig 3: Dip pattern and time of onset of asthma exacerbation

Fig 2a: Dip patterns in asthmatic children showing evening

dip

5

3

Discussion

Furthermore, regular patterns of dip is frequently seen in

asthmatics than the control. This reflects the fact that the

amplitude of variation is greater in asthmatics than in

normal subjects, since wide amplitude is required to

This study is in agreement with the fact that a rhythm in

respiratory function_,₉_,₁d₀oes exist in asthmatic and non-

5

15

asthmatic subjects.

However, this rhythm or diurnal

demonstrate this regular patterns. Thus, with good con-

variability is less readily detected in healthy, non-

asthmatic subjects while more readily detected in asth-

matic subjects. In the current study majority of the asth-

matic subjects (97.6%) showed a discernable pattern of

variability, while only 2.2% of normal controls exhib-

ited this attribute.

trol of asthma, the pattern of variability may not be so

discernable among the asthmatics. This was further sup-

ported by the findings of Connolly, that treatment with

bronchodilators reduce the variability in PEFR among

asthmatics and the various dip₁₅patterns were no longer

seen in some of the asthmatics.

The exact mechanism of circadian rhythm in the airways

is not clear. I₁t_,₂_,h₁₁as been found to be unrelated to bron-

The time of dip may be relevant in deciding the possible

aetiologic factor in asthmatics and may be relevant in

finding the location of the trigger factors. For instance,

those who their asthma is attributed to house dust mites

in beddings may be more likely to have evening or early

morning dip. But this was not supported by the findings

of Clark and Hetzel who demonstrated the va₉rious dip

patterns in both atopic and non-atopic subjects.

chial calibre,

rather, it represents bronchial reactiv-

ity. This is corroborated by the finding of a diurnal

variation₁_,₂i_,n₁₁airway sensitivity to histamine and to acetyl-

choline.

This bronchial reactivity is modulated by

several inputs and through multifactorial control systems

1

,2,3,11

including catecholamines and endogenous steroids.

Various patterns of the rhythmicity are_,₆ demonstrable,

Considering the likelihood of patients having an acute

attack and in some cases life threatening attack which

may start suddenly and become severe within a short

time. The analysis of the various dip patterns becomes

useful to both the physician and the pat₄ient in predicting

5

with morning dip being the commonest. Generally, the

time of trough was at 6am and acrophase at 2pm. As

these patterns differ from healthy subjects, determina-

1

1-13

tion of dip pattern may aide in the care of asthma.

1

This is of particular importance in resource poor areas

where sophisticated methods are unavailable for asthma

diagnosis since determination of circadian rhythm is

performed with the P₁₂e_,₁a₃k Flow Meter, which is cheap

and readily available.

onset of such life threatening attacks. In this instance,

the drug treatment of such patient could be adjusted to

adequately cover the period of dip. Drugs like the long-

acting bronchodilators being used up to twice daily may

effectiv₁e₄ly do this and reduce the risk of life threatening

attacks.

The fact that it is easier to demonstrate rhythmicity in

the changes of the airway calibre among asthmatics than

the non-asthmatics may be connected to the initiation

and propagation of an acute attack of asthma and the

effect of this heightened rhythmicity in asthmatics may

become obvious when their airway is exposed to trigger

factors (which other individuals may be exposed to

without effect). This leads to a cascade of effects, in-

cluding an initial cholinergic bronchoconstriction and

activation of release of bronchoconstrictors and inflam-

matory ₄peptides from the airway cells and sensory

From the foregoing, the dip pattern is a possible indica-

tion of the lability of the airway of the asthmatic. In line

with this, an asthmatic without a discernable pattern has

a more stable airway with less likelihood of an acute

attack. Furthermore, a morning dipper has a labile air-

way in the morning or on waking and such an asthmatic

may not have been compliant with his drugs or the drugs

may have worn-out from the system, thereby leaving

such periods uncovered with drugs. In essence, a double

dipper asthmatic has more likelihood of developing pos-

sible acute attacks at more times than either the morning

or evening dipper and this may show poor asthma con-

trol for such a subject. Interestingly, interpretation of the

findings of this study c₁o₄_,u₁₅ld find several use in different

aspects of asthma care.

1

nerves. This will lead to contraction of the smooth

muscle and later oedema of the airway due to plasma

exudation from the vessels caused by the inflammatory

1

4

mediators. When this acute response is initiated on an

excessively labile airway, there could be rapid onset₁o₄f

acute airway obstruction in a previously stable patient.

Further studies may be needed to correlate some of this

findings with the level of control of asthma in these

asthmatics and possibly the effects of drugs on the pat-

tern demonstrated.

Several specific clinical applications and interpretations

concerning the diagnosis, monitoring and management

of asthmatics, either during acute exercitations or even

at steady state are derivable from this study. For in-

stance, acute exacerbations are more likely to occur in

the morning or at the time of lowest PEFR values

Study limitations

(

drugs and use of inhalers should be tailored to reflect

this. This confirms contention by Hetzel that there is a

reduced airway calibre) and as such the dosage of the

•

We relied on the PEFR recording done at home.

Although we tried to authenticate each recording

done at home, this was still a limitation as some

may be tempted to falsify result if they forgot to do

it at the right time.

1

pulmonary clock. Interestingly, this pu₁_,l₉m_,₁₅onary clock is

operation both in disease and in health.

5

4

•

We studied children as young as five years, hoping

that their parents will supervise them, but instruct-

ing children of this age group is difficult.

In getting time of onset of attack, we relied on the

patient’s account of such attack. Sometimes, decid-

ing when an attack started is difficult.

However, the proportion of asthmatics with dip pattern

is far more than that in non-asthmatic children. From

this study, the airway calibre measured by the PEFR was

smallest in the morning at 6am and largest in the after-

noon at 2pm.

At each time of the day, the asthmatics had lower PEFR

or smaller calibre than healthy children.

Further research areas

Due to the wider variation in airway calibre among the

asthmatics, the difference between the airway at differ-

ent times of the day reflecting in their dip patterns was

more discernable in the asthmatics than in healthy chil-

dren.

•

In future, to ensure adequate monitoring, a similar

study could be done on recuperating asthmatics on

admission in the hospital using other children in the

hospital that are non-asthmatics as control.

Allergic skin test could be included for the asthmat-

ics to find out what they are exposed to that is caus-

ing the attack at different times of the day.

Effect of drugs on these various dip patterns.

This study can be done on asthmatics during acute

attack.

•

Authors’ contribution

Oviawe O : Study design, data collection and analysis,

and supervision

Osarogiagbon W: Data collection, analysis and write up

Conflict of Interest: None

•

Funding: Authors

Conclusion

The airway calibre varies with the time of the day both

in normal children and in the asthmatics. These variation

References

1

2

3

.

Hetzel MR, Clark TJH, Houston

K. Physiological patterns in early

morning asthma. Thorax 1977; 32:

6. Lebowitz MD, Krzyzanowski M,

11. Van-Alderen WMC, Postina DS,

Koeter GH, Knol K. Nocturnal

airflow obstruction, histamine and

the autonomic central nervous

system. Thorax 1991; 46: 366 –

371.

12. Cockcroft DW, Hargreaves FE.

Airway hyper-responsiveness:

relevance of random population

data to clinical usefulness. Am.

Rev. Resp. Dis. 1990; 142: 497 –

500.

13. Bellia V, Cibella F, Coopola P,

Greco O, Insalac O, Milone F, et

al. Variability of peak expiratory

flow rate as a prognostic indicator

in asymptomatic asthma. Respira-

tion 1984; 46: 328 – 333.

14. Ayresa JG, Milesa JF, Barnesb, PJ.

Brittle asthma. Thorax 1998; 53

(4):315-321.

Quackenboss JJ, Rourke MK. Diur-

nal variation of PEFR and its use in

epidemiological studies. Eur. Resp.

J. 1997; 24: S49 – S56.

7. Connolly CK. House dust mite

hypersensitivity: Morning dipping

and severity of wheeze. Respiration

1981; 42: 258 – 262.

8. Thomas F, Rolf M, Radvan U,

Joachim K. Variability of PEFR in

children; short and long term repro-

ducibility. Thorax 1995; 50: 35 –

39.

9. Clark, TJH, Hetzel MR. Diurnal

variation of asthma. Br. J. Dis.

Chest 1977; 71: 87 – 92.

4

18 – 423.

Lewinshohn HC, Capel LH, Smart

J. Changes in forced expiratory

volumes throughout the day. Br.

Med. J. 1960; 1: 462 – 464.

Mark B, Donald YM. Allergic

disorders. In: William WH, An-

thony RH, Myron JL, Judith MS.

(eds) Current Pediatric Diagnosis

and Treatment. London: Lange

Medical Books/McGraw-Hill, Ltd,

2

001; 939 – 943.

4

5

.

Martin-Cicutto LC, Smith HR.

airway inflammation, nocturnal

asthma. Am. Rev. Resp. Dis. 1991;

10. Albertini M, Politano S, Berard E,

Boutte P, Mariami R. Variation in

peak expiratory flow of normal and

asymptomatic asthmatic children.

Paediatr. Pulmonol. 1989; 7: 140 –

144.

1

43: 351 – 357.

Hetzel MR, Clark JJ. Comparison

of normal and asthmatic circadian

rhythms in peak expiratory flow

rate. Thorax 1980; 35: 732 – 738.

1

5. Connolly CK. Diurnal rhythms in

airway obstruction. Br J Dis Chest

1

979; 73:357–366.