Journal clubJournal clubYassin M. Alsaleh

Supervised by: Dr.Sameer Al Abdi

بسم الله الرحمن الرحيم)وكلوا واشربوا وال تسرفوا انه ال يحب

المسرفين(eat and drink: but waste not by excess, for

Allah loveth not the wasters

INTRODUCTIONINTRODUCTION• Asthma is one of the most common chronic

inflammatory conditions that affect children.• The prevalence of asthma and allergic diseases

has increased dramatically over the past few decades .

• cause of airway inflammation is multifactorial and involves many of cell types and inflammatory mediators.

INTRODUCTIONINTRODUCTION• Despite many therapeutic advances asthma

continues to result in significant childhood morbidity .

• There has been a considerable interest in the potential therapeutic and protective value of dietary supplementation to decrease incidence of asthma.

omega-3 fatty acids omega-3 fatty acids

• omega-3 fatty acids are incorporated into cellular membranes of all tissues.

Vitamin CVitamin C

• Vitamin C is an antioxidant free-radical scavenger present in intracellular and extra-cellular lung fluids.

ZincZinc

• Zn is an important element in the preservation of immune resistance and plays an important role in DNA and protein synthesis also as a cofactor .

ObjectivesObjectives

• The aim of this work is to investigate the beneficial role of omega-3 fatty acids, vitamin C and Zn diet supplementation in asthmatic children either as a single supplement or in combination.

METHODOLOGYMETHODOLOGY• 76 children between 7 and 10 years of age

(suspected of having moderate persistent bronchial asthma and attending the Asthma Clinic of Paediatric Department.

• children were randomly allocated using computer-generated list of random numbers from March 2007 to November 2007.

• Twelve of them were excluded due to failure to trace them, and four were excluded due to the intake of

anti- leukotrienes.

METHODOLOGYMETHODOLOGY• Exclusion criteria

1. Any chronic diseases other than asthma and rhinitis.

2. Intake of antileukotrienes during the study.

3. Children taking polyunsaturated fatty acid (PUFA) or antioxidants supplements above the levels recommended for adequate intake, or regularly consumed more than one fish meal per week.

4. Manifestations of vitamin C or Zn deficiency.

METHODOLOGYMETHODOLOGY• randomized, double blind, placebo-self-

controlled crossover trial over 38 week.• All children 76 entered the study on their

normal diet (phase 1).• after which all the children entered five

different therapeutic phases, each of 6-week duration in a random sequence.

• observers, subjects and families being blinded to which treatment was being given at which time.

METHODOLOGYMETHODOLOGY• Every therapeutic phase is followed

by a 2-week washout period.

• Each child got each treatment phase, one after the other in random order.

• By the end of the study, all children had been exposed to the five treatment phases (including the placebo).

METHODOLOGYMETHODOLOGY

Study Design:

PHASES:PHASES:

• In the placebo phase:(normal diet plus three placebo identical appearing capsules containing lactose).

• In the omega 3 phase :( normal diet plus one capsule per day containing 1000 mg of a triglyceridic oil and two placebo capsules containing lactose).

• In Zn phase, ( normal diet plus daily one capsule containing 15 mg Zn and two placebo capsules) .

• In vitamin C phase:normal diet plus daily one capsule containing 200 mg ascorbic acid and two placebo capsules)

• in the combined treatment phase: normal diet supplemented daily with one capsule containing triglyceridic oil one capsule containing Zn and one capsule containing ascorbic acid.

PHASESPHASES

placebo phase

omega 3 phase

Zn phase

phase 6

vitamin C phase

combinedtreatment phase

Normal diet 3 placebo

Normal diet 2 placebo Omega 3

Normal diet 2 placebo Zn

Normal diet 2 placebo vitamin C

Normal diet vitamin CZnOmega 3

Pre- treatment phase

Triple assessmentTriple assessment

• The primary end point of this trial was improvement of the lung function.

• triple assessment as follow:1. Subjective: by childhood asthma control test (C-ACT).

2. Physiological: by pulmonary function test.

3. Inflammation by: (i) sputum differential cell count,esinophil percentage. (ii) sputum inflammatory mediators.

RESULTS :RESULTS :

RESULTS

Childhood asthma control test:RESULTS

Childhood asthma control test:• There was no statistical difference between

the pretreatment phase and placebo as regard to C-ACT (p = 0.2 and 95% CI of 0.06 [−0.25, 0.38]).

• while there was a significant improvement of the score in all four treatment phases when compared to the pre-treatment and placebo phases (p < 0.001)..

• It increased from (16.5 ± 1.66) to (22.1 ± 2.02) in the phase where the patients were supplied omega3, Zn and vitamin C all together (p < 0.001).

RESULTS Pulmonary function tests:RESULTS Pulmonary function tests:

• The FEV1 showed no significant difference between pretreatment and placebo phases (p = 0.08 95% CI of 7.1[−0.13, 14.3])

• Both FEV1 and FEV1/FVC ratio showed statistically significant improvement in all four treatment phases when compared to the pre-treatment and placebo phases (p< 0.001).

• They also showed statistically significant improvement in phase 6 with the use of the three substances than other mono-therapy phases (p < 0.001)

RESULTS Sputum analysis:RESULTS Sputum analysis:

1-Cellular element:• The total sputum WBC showed no significant

difference between pre-treatment and placebo phases (p = 0.7)

• while there was a significant decrease of the count in all four treatment phases.

• It also significantly decrease in phase 6 than any of the other three treatment phases with mono supplementation (p < 0.001)

RESULTSRESULTS

2-Inflammatory mediators:• All the inflammatory mediators showed no significant

difference between pre-treatment and placebo phase (p > 0.05;).

• Sputum LTE4-C4 and LT1B showed a significant reduction in all four treatment phases when compared to the pretreatment phase .

• It also showed significant decrease in phase 6 than in the other three mono supplementation phases (p < 0.001).

Critical apprasial

PICOPICO• Population: children between 7 and

10 years of age (suspected of having moderate persistent bronchial asthma .

• Intervention: omega-3 fatty acids, vitamin C and Zn

• Control: placebo.

• Out come: improvement of the lung function.

Relevance Relevance

1. Does the study address a common problem in your practice?

2. Does the study address an important outcome to you

or to your patient? (DOE vs. POEM).

3. Assuming that the study conclusion is true would it lead to a change in your practice?

ValidityValidity

1. Was the assignment of patients to treatment randomized?

Yes

2- Was the assignment concealed?

Yes

ValidityValidity

3- Were patients analyzed in the groups to which they were randomized (intention to treat analysis)?

N/A• Was follow-up complete& long enough?

,• Sensitivity analysis (WCS)

ValidityValidity

3. Were the groups similar at the start of the trial? Baseline prognostic factors (demographics, co-morditity, disease severity, other known confounders) balanced?

N/A4. Were patients, their clinicians, and study personnel

'blind' to treatment?

ValidityValidity

5. Aside from the experimental intervention, were the groups treated equally?

• Co-intervention?

• Contamination?

• Compliance?

ValidityValidity

6. Were all clinically important outcomes considered?

Results clinical significanceResults clinical significance

• Risk difference (ARR)

= |EER-CER|

• Risk Ratio (RR)?

• Relative risk reduction (RRR)?

= |EER-CER|/CER

• NNT ?

=1/ABI

NOT DONE

Results clinical significanceResults clinical significance

• Precision of the effect: • Confidence intervals?

•

Applicability Applicability

1. Can you do the Intervention exactly as it is described in the paper

we can’t till

2. Is your Patient is similar to the population of the study?

3. Are the likely treatment benefits worth the potential

harms and costs? we can’t till

CONCLUSIONCONCLUSION• Children with moderately persistent bronchial asthma may get

benefit from their diet supplementation with omega-3 fatty acids, Zn and vitamin C.

• This study showed that their asthma control test, pulmonary function tests and pulmonary inflammatory markers showed significant statistically improvement with these diet supplementation.

• Further studies of different age groups, and different degrees of asthma severity are needed.

appendages

http://www.asthmacontrol.com/child.html

SpirometrySpirometry• (meaning the measuring of

breath) is one of the Pulmonary Function Tests (PFTs), measuring lung function, specifically the measurement of the amount (volume) and/or speed (flow)

• Spirometry is an important tool used in assessing conditions such as asthma, pulmonary fibrosis, cystic fibrosis, and COPD.

• Forced Vital capacity (FVC)• Total amount of air that can be blown out after

a maximal deep breath, as fast as you can. • Forced Expired Volume in One second

(FEV1)• The amount of air that can be blown in the first

second in the FVC maneuvere.

Crossover studyCrossover study• A crossover trial also referred to as a crossover

study is a clinical trial in which patients are given all of the medications to be studied, or one medication and a placebo in random order.

• These studies are generally done on patients with chronic diseases to control their symptoms.

• A crossover study has the advantage over a simple double-blind study that the variability between patients is minimized because each patient crossing over in effect serves as their own control.

Crossover studyCrossover study• One disadvantage is that long term effects

cannot be tracked with this approach.• Another disadvantage is that curative

therapies cannot be tested after one another or before a placebo.

• the issue of order effects, because it is possible that the order in which treatments are administered may affect the outcome. An example might be a drug with many adverse effects given first, making patients taking a second, less harmful medicine, more sensitive to any adverse effect.

Related tablesRelated tables

•sm001.doc

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