General overview of how to criticize a research article

1. Journal Reporting
Dr. Pravinkumar A. Wahane
JR II, Dept. Of Pharmacology
B.J.G.M.C. Pune

2. A randomized, double-blind, placebo
controlled trial of oral montelukast in
acute asthma exacerbation
Ali Bin S Z, Nawal S, Ali K, Safia A et al.
BMC Pulmonary Medicine 2013, 13:20, 1-7

3. Introduction
 Asthma associated with chronic airway inflammation with
recruitment of a number of inflammatory cells including T-cells,
mast cells and eosinophils
 Ranked as major contributor to emergency department
visits
 Incidence is on rise all across world, especially in paediatric
population, with bronchial asthma accounting for 4% of the
paediatric out-patient visits

4. Introduction
 Interaction of these mediators with the Type 1 cysteinyl
leukotriene receptors (CysLT-1), located on inflammatory
cells and structural cells of airways implicated in :
 Inflammatory cell infiltration,
 Initiation of bronchial smooth muscle contraction,
 Mucus secretion and
 Increased vascular permeability
Ultimately leads to airway narrowing
 Montelukast is M.C. used (CysLT-1) antagonist

5. Introduction
 Shown to improve symptoms & lung function (FEV1) within
15 minutes of administration in chronic asthma with its
effects lasting for a period of at least 24 hours
 Existing therapeutic modalities for acute asthma include
oxygen and short acting β2 agonist bronchodilators in
order to promptly reverse airflow obstruction
Hypothesis
 Treatment with a leukotriene receptor antagonist (LTRA),
montelukast sodium would improve airway obstruction
and clinical outcomes in acute asthma exacerbation and
would subsequently decrease the duration of hospital stay

6. Materials and Methods
 Randomized, double-blind, placebo controlled parallel
group drug trial conducted over a period of two years from
February 2006 to February 2008 in Tertiary care hospital
 Patients presenting to the emergency department with
acute asthma exacerbation were included in study after
primary screening
 Ethics Review Committee approval was Obtained
 Informed Consent obtained from subjects before inclusion
in the study

7. Materials and Methods
Inclusion Criteria
 Diagnosis of acute asthma exacerbation that required
hospitalization as defined by the Global Initiative for
Asthma (GINA) Guidelines
 Pts. with FEV1 < 70% predicted aged 16 yrs or more
 Pts. with PEF < 300 L/min aged 16 yrs or more
 After receiving 30 minutes of initial treatment in the ER
 Respiratory rate > 24 breaths/min
 No improvement in symptoms such as shortness of breath
or wheezing

8. Materials and Methods
Exclusion Criteria
 Age <15 years , Pregnancy
 FEV1 > 70% predicted OR PEF > 300 L/min
 History of tobacco use of >10 years
 Concomitant therapy with systemic Corticosteroids or
leukotriene modifiers at any time in the past 4 weeks at the
time of admission
 Any concurrent acute medical condition like AMI, CCF, DKA
or Shock
 Acute respiratory failure requiring mechanical ventilation

9. Study Procedure
 Patients were assigned to Treatment group (Montelukast)
and Placebo group randomly by computer generated
randomization sequence
 Patients in Group 1 (Treatment Group) : -
 Received standard therapy & oral montelukast sodium
(10 mg once daily)
 Patients in Group 2 (Placebo Group) :-
 Received standard therapy along with a placebo

10. Study Design

11. Outcome Assessment
 Primary Outcomes
 Improvement in lung function measured as PEF and
FEV1 over the course of hospital stay and discharge
 Duration of hospital stay
 Secondary Outcomes
 Development of complications such as :
 Respiratory failure,
 Cardiac arrest and/or
 Death

12. Statistical Analysis
 Categorical variables were analyzed using Chi-square
test
 Continuous variables were analyzed using Fisher exact
 All analyses were conducted by using the Statistical
package for social science (SPSS Release 15.0)
 p-values were considered as statistically significant
if < 0.05

13. Results : Baseline Characteristics

14. Results : Baseline Characteristics

15. RESULTS

16. Primary outcome measures
 No significant difference in the PEF between both
treatment groups during the hospital stay and at
discharge
 No Statistically significant difference in Mean PEF of
Montelukast and Placebo groups at time of discharge
 No Statistically significant difference in Mean FEV1 in
Montelukast and Placebo groups at time of discharge
 Mean duration of Hospital stay for patients belonging to
montelukast and placebo groups was 3.67 ± 1.86 days and
3.72 ± 2.02 days respectively (p – 0.90)

17. Primary outcome measures

18. Primary outcome measures

19. Secondary outcome measures
 Two patients, one from each arm, developed
respiratory failure
 No patient in either group was withdrawn due to
worsening asthma or adverse drug effect from the
study

20. Discussion
 Study did not reveal significant differences in :
 PFTs measured as FEV1 at admission and discharge &
PEF measured at specific intervals
 Length of hospital stay in patients hospitalized with
acute asthma exacerbation that were given oral
montelukast vs. placebo
 Efficacy and tolerability profile of oral montelukast were
comparable to placebo and no serious adverse effects were
encountered
 Study findings were not consistent with Ramsay et al,
Silverman et al, Camarago et. al. & Adaichi et. al.

21. Conclusion
 Study suggests that there is no added benefit of using
montelukast along with the standard therapy for the
management of acute asthma exacerbation in
hospitalized adult population
 Larger scale multicentre trials needed to better evaluate
the role of cysteinyl leukotriene's antagonists in treating
acute exacerbations of asthma

22. Comments
 Clinical Trial Registration No. - Mentioned
 Title – Gives clear idea about aim and study design but not
about the dosing pattern / route of administration of
Montelukast
 Introduction – Background information and purpose of
study mentioned
 Materials and Methods – Ethical Approval and informed
consent has been obtained
 Place ,Duration of study and Study design mentioned
 Randomization method & inclusion / Exclusion criteria
mentioned

23. Comments
 Source of Drug – Mentioned
 Results – Statistical Test applied mentioned, Statistical
software used for analysis mentioned, appropriate tables
and figures included
 Discussion – Results repeated, Relevant studies mentioned,
Limitations of the study mentioned
 Results - Emphasizes need for further studies regarding
Montelukast use in acute exacerbation of asthma
 Supports and Conflict of Interest - Mentioned as Nil