Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma

Sapna Charania, Mercer University College of Pharmacy

Many children younger than 12 years of age receive acetaminophen each week, making it the most commonly used pediatric medication in the United States. [1] Observational studies have shown an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma. [2,3]

Depletion of glutathione in the respiratory tract by acetaminophen and the resulting loss of antioxidant protection in the lung have been suggested as possible mechanisms for the positive association between frequent acetaminophen use and asthma-related complications. [4]

Airway inflammation is considered to be a dominant feature of asthma. It is speculated that an anti-inflammatory agent such as ibuprofen could offer some protection in the presence of an acute febrile illness. In young children, anti-inflammatory medications might modulate the immune response to allergens.   Viral infections during childhood are considered to initially promote a TH1-type, or non-allergic, lymphocyte response, but during the resolution of the illness, a localized TH2, or allergic, lymphocyte response is suggested to predominate, and simultaneous allergen exposure is suggested to enhance the development of TH2 memory lymphocytes. [5]

Aspirin and possibly other non-steroidal anti-inflammatory drugs have been shown to block the TH2 response. This mechanism has been hypothesized to explain the increase in allergic illness in children, including asthma, which has been observed subsequent to the discontinuation of aspirin use in pediatrics. [6]

However, appropriately designed randomized trials that have prospectively evaluated the association between the standard use of acetaminophen for children and asthma symptoms are found to be lacking. Since both acetaminophen and ibuprofen are reported to be commonly used and suggested to be the only readily available agents for fever or pain in young children, the authors of this study sought to investigate whether the use of acetaminophen, was associated with higher morbidity related to asthma than that with ibuprofen, among children 12 to 59 months of age who have mild persistent asthma. [7]

 

 

Title: Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma [7]

 

Design Multicenter, prospective, randomized, double-blind, parallel-group; N= 300
Objective To investigate whether the use of acetaminophen, when clinically indicated, was associated with higher morbidity related to asthma than that with ibuprofen in young children with mild persistent asthma
Study Groups Acetaminophen (n= 150), ibuprofen (n= 150)
Methods Acetaminophen was administered at a dose of 15 mg per kilogram of body weight every six hours as needed, and ibuprofen was administered at a dose of 9.4 mg per kilogram of body weight every six hours as needed.
Duration March 2013 through April 2015
Primary Outcome Measure Number of asthma exacerbations that led to treatment with systemic glucocorticoids
Baseline Characteristics
  Acetaminophen

 

Ibuprofen
Age — months ± SD 40.3 ± 12.9

 

39.4 ± 13.6

 

Male sex — no. (%) 86 (57)

 

93 (62)

 

Race or ethnic group — no. (%)    
White 74 (49)

 

74 (49)

 

Black

 

47 (31)

 

50 (33)

 

Hispanic or Latino 35 (23)

 

37 (25)

 

Oral glucocorticoid courses in the previous 6 months — no. ± SD 1.01 ± 1.06

 

1.15 ± 1.04

 

Albuterol inhalations per week — no. ± SD 1.81 ± 3.49

 

1.50 ± 2.22

 

Use of inhaled glucocorticoids in the previous 12 months — no. of patients (%) 92 (61)

 

86 (57)

 

Use of leukotriene receptor antagonist in the previous 12 months — no. of patients (%) 22 (15)

 

39 (26)

 

Results
No. of asthma exacerbations that led to treatment with systemic glucocorticoids-no. of patients (%) Acetaminophen

 

Ibuprofen Relative Rate

(95% Confidence interval)

P-value
0 76(51)

 

78(53)

 

 

 

 

1 42 (28)

 

34 (23)

 

 

 

2 16(11)

 

21(14)

 

 

 

≥3 16 (11)

 

15 (10)

 

 

 

Mean exacerbation frequency over 46 weeks (95% Confidence Interval)

 

0.81 (0.65 to 1.02)

 

0.87 (0.69 to 1.10)

 

0.94 (0.69 to 1.28)

 

0.67
Adverse Events
Common Adverse Events- no. (%) Ibuprofen

 

Acetaminophen

 

 

Acute

nasopharyngitis

15 (10%)

 

9 (6%)

 

Acute pain 41 (27%)

 

59 (39%)

 

Allergic rhinitis 35 (23%)

 

43 (29%)

 

Allergy, unspecified

 

28 (19%)

 

28 (19%)

 

Asthma with (acute) exacerbations 5 (3%) 9 (6%)
Cough 54 (36%) 54 (36%)
Diarrhea 30 (20%)

 

32 (21%)

 

Headache

 

75 (50%)

 

92 (61%)

 

Strep sore throat

 

28 (19%)

 

29 (19%)

 

Wheezing

 

16 (10%) 17 (11%)
Serious Adverse Events-no. (%)    
Influenza 1 (0.6%)

 

Pneumonia

 

1 (0.6%)
Asthma Exacerbation 6 (4%) 3 (2%)
Wheezing/Hypoxia 1 (0.6%)

 

Constipation 1 (0.6%)

 

Bronchitis 1 (0.6%)

 

Chronic Tonsillitis and Adenoiditis 1 (0.6%)

 

Simple laceration of simple mucosa

 

1 (0.6%)
Cough 1 (0.6%)

 

Status Asthmaticus

 

1 (0.6%)
Percentage that discontinued due to adverse events 2.6 0.6
 
Study Author Conclusions Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen.

 

This trial enrolled children aged 12 to 59 months, who had mild persistent asthma and who were receiving treatment with asthma-controller therapies. These results may not be applicable to other age groups or to patients who have moderate or severe asthma that requires treatment with a higher level of asthma-controller medications.

The findings of this study are in contrast to those of a post hoc analysis of a randomized trial that showed that the relative risk of unscheduled visits for asthma was substantially higher in the weeks after taking acetaminophen for febrile illness than in the weeks after taking ibuprofen (relative risk, 1.79). [4]

Another noteworthy finding of this study was that greater use of antipyretic, analgesic medications such as acetaminophen and ibuprofen was associated with more apparent respiratory illnesses and that the reported respiratory illnesses were associated with asthma exacerbations that led to treatment with systemic glucocorticoids.

References

  1. Vernacchio L, Kelly JP, Kaufman DW, Mitchell AA. Medication use among children <12 years of age in the United States: results from the Slone Survey. Pediatrics. 2009;124(2):446-54.
  2. Beasley R, Clayton T, Crane J, et al. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme. Lancet. 2008;372(9643):1039-48.
  3. Beasley RW, Clayton TO, Crane J, et al. Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three. Am J Respir Crit Care Med. 2011;183(2):171-8.
  4. Lesko SM, Louik C, Vezina RM, Mitchell AA. Asthma morbidity after the short-term use of ibuprofen in children. Pediatrics. 2002;109(2):E20.
  5. Varner AE. The cyclooxygenase-2 theory of atopy and asthma. Pediatr Asthma Allergy Immunol. 1999;13 :43– 50.
  6. Varner AE, Busse WW, Lemanske RF. Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma. Ann Allergy Asthma Immunol. 1998;81:347– 351.
  7. Sheehan WJ, Mauger DT, Paul IM, et al. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med. 2016;375(7):619-630.

 

 

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