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CURRENT TOPIC IN EPIDEMIOLOGY
BY UCHECHI OKANI
EPIDEMIOLOGY, HEALTH PROMOTION, AND RESEARCH
IN ADVANCED NURSING PRACTICE
TEXAS WOMAN’ S UNIVERSITY FEBRUARY 12, 2011
» The New York Times Reprints
» .
» August 16, 2010
» Risks: A Warning on Asthma and Acetaminophen
» By RONI CARYN RABIN
» Young teenagers who use acetaminophen even once a month develop asthma symptoms more than twice as often as those who never take it, a large international study has found. And frequent users also had more
eczema and eye and sinus irritation.
» Other studies have linked acetaminophen (often sold as Tylenol and in other over-the-counter remedies for pain, colds, fever and allergies) with an increased risk of asthma. But the new study’s authors cautioned that the findings did not mean children should stop using it.
» Source: http://www.nytimes.com/2010/08/17/health/research/17risk.html?_r=1&pagewanted=print
» CNN.com »
» Study: Acetaminophen may double asthma risk in kids
» By Denise Mann, Health.com
» August 13, 2010 12:51 p.m. EDT
» (Health.com) -- Teenagers who take acetaminophen -- the active ingredient in Tylenol and many other over-the-counter remedies -- may be at increased risk of asthma and some allergic conditions, according to a new study of more than 320,000 children in 50 countries.
» Compared with those who never take the popular pain reliever and fever reducer, 13- and 14-year-olds who take acetaminophen at least once a month are 2.5 times more likely to experience asthma symptoms, the study found. Even those who take acetaminophen just once a year are 40 percent more likely to experience symptoms.
» Kids who take acetaminophen may also be at greater risk of certain allergic conditions. Once-a-month users were roughly twice as likely as never users to have eczema, a stuffy nose (rhinitis), and itchy and watery eyes, according to the study, which was published on the website of the American Journal of Respiratory and Critical Care Medicine.
» Source:
http://www.cnn.com/2010/HEALTH/08/13/acetaminophen.may.double.asthma.risk/index.html
» Acetaminophen (paracetamol): » Very common over the counter (OTC) drug in the U.S.A.
» Use:
» Mild-to-moderate pain and fever (analgesic/antipyretic)
» Mechanism of action:
» Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
» Some U.S. Brand names: » Tylenol, Acephen, Cetafen, Excedrin Tension Headache, Feverall
etc.
» Dosage: » Neonates: 10-15mg/kg PO/PR q 6-8h prn
» Infants/children: 10-15 mg/kg PO/PR q 4-6h prn
» >12 y o: 325 – 650mg PO/PR q 4-6h prn; max 4g/day
» Source: Uptodate (2011). Acetaminophen (paracetamol): Drug information. Retrieved from http://www.uptodate.com/contents/acetaminophen-paracetamol-drug-information?source=search_result&selectedTitle=1~150
» What i s ast hma?
» Source: CDC (2011). Asthma: Management and Treatment. Retrieved from http://www.cdc.gov/asthma/management.html
Asthma is a chronic disease of the airways that may cause:
» Breathlessness
» Wheezing
» Chest tightness
» Nighttime or early morning coughing
» PATHOPHYSIOLOGY OF ASTHMA
» The pathophysiology of asthma is complex and involves the following:
» Airway inflammation
» Intermittent airflow obstruction
» Bronchial hyperresponsiveness
» The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the
presence of airway edema and mucus secretion also contributes to airflow obstruction and
reactivity (8)
» Source: National Heart Lung and Blood Institute Diseases and Conditions Index(NHLBI) (2011). Asthma. Retrieved From
http://www.nhlbi.nih.gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html
Ast hma epi demi ol ogy
» Source: CDC (2011). Asthma: Data and Surveillance. http://www.cdc.gov/asthma/asthmadata.htm
Asthma prevalence
Worldwide estimates
» In 2004, 300 million people worldwide had asthma (4)
National Estimates
» From 1980 to 1996, asthma prevalence grew from 3.5% to 5.5%, an annual percentage increase of 3.8% (1)
» From 2001--2003, an average annual 20 million persons in the United States had asthma (7)
» The annual percentage increase from 2001 to 2009 was 1.2% (1)
Asthma prevalence cont.
National Estimates cont.
» In 2007, 34 million (11.5%) Americans had asthma (4)
˃ 9.6 million Children (13.1 %) < 18 years (4)
˃ 24.4 million Adults, 18 and older (10.9 %) (4)
» In 2009, 24.6 million Americans had asthma (prevalence of 8.2% of the U.S. population ) (1)
˃ 17.5 million non-institutionalized adults (3)
˃ 7.1 million children (9.6%) (3)
Mortality: » Worldwide Death by asthma » In 2004: 255,000 (4)
» Deaths in the U.S. by asthma:
» 2001 – 2003: 4,210 average annual deaths from asthma (7)
» In 2007: 3,447 deaths from asthma (4)
» higher among adults than among children
» Higher among women (2173) than in men (1,274) (4)
*National Asthma related cost and expenditure
» In 2007, > $30 billion (includes the direct expenditure of treating
asthma) (4)
Health Care use » From 2001--2003, an average annual 12.3 million physician visits
for asthma (7)
» In 2006:
˃ ~ 444,000 hospital discharges related to asthma, with an
average length of stay of 3.2 days (4)
˃ 1.1 million Hospital outpatient visits (4)
˃ 1.6 million Emergency department visits (4)
˃ 10.6 million asthma-related visits to physicians (4)
» In 2007, there were 1.75 million asthma-related emergency
department visits and 456,000 asthma hospitalizations (1).
» In 2008, persons with asthma missed 10.5 million school days and
» 14.2 million work days due to their asthma (1).
PROBLEM: » Increase in world-wide prevalence of asthma in recent
decades
» The patterns of asthma prevalence not adequately explained by current knowledge of the causation of asthma
» Use of Paracetamol named a risk factor for development of asthma
» The change from use of aspirin to paracetamol in children in the U.S. in the 1980s was followed by increasing prevalence during this period
» Hypothesis:
» Exposure to Paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma (6)
Research
» Population-based Avon Longitudinal Study of Parents and Children (ALSPAC)
» Findings:
» The frequent use of paracetamol in late pregnancy (20–32 weeks) was associated with a twofold increased risk of wheezing in children at 3 years (6).
» The frequent use of paracetamol in late pregnancy was associated with an increased risk of persistent wheezing compared with no use .(6)
» Paracetamol use in pregnancy and risk of childhood asthma
» Source: Farquhar, H., Stewart, A., Mitchell, E., Crane, J., Eyers, S., Weatherall, M., and Beasley, R. (2010). The role of paracetamol in the pathogenesis of asthma. Clinical & Experimental Allergy, 40 (1), p32-41. Retrieved on February 3, 2011, from Health Source: Nursing/Academic Edition database.
Country Year of
publication
Exposure in
pregnancy
Comparison Sample size
(n)
Age of Children Outcome
Odds ratio (95%
confidence interval)
United
kingdom
2002 20-32
weeks
Most days/daily
vs. no use
9400 3years Current wheezing 2.10(1.30-3.41)
United
Kingdom
2005 8511 6-7 years 1.86 (0.98-3.55)
Denmark 2008 During
pregnancy
Ever use vs. no
use
66455 18 mo Wheezing ever 1.13 (1.10-1.17)
12733 7 years Persistent
wheezing
1.37 (1.07-1.75)
Singapore 2007 During
pregnancy
Ever use vs. no
use
34 3-10 years Allergic asthma
35% vs. 0%, p=0.03
Spain 2008 During
pregnancy
At least once per
month vs. no use
1741 3–5 years Current
Wheezing
1.71 (1.15–2.53)
United
States
2008 During
pregnancy
Ever use vs.
no use
345 1 year Current
Wheezing
1.8 (1.1–3.0)
United
States
2008 During
pregnancy
Ever use vs.
no use
280 5 years Current
Wheezing
1.7 (1.2–2.2)
» Research:
» Koniman and colleagues (2007) investigated the association between paracetamol usage during pregnancy and the first 6 months of life, and childhood allergy, allergic asthma, and asthma, using a matched patient-sibling study comparing patients with allergic asthma with their healthy siblings without any symptoms of allergic diseases.
» Findings:
» Usage of paracetamol in pregnancy was associated with allergic asthma. Usage between birth and 6 months of age, and between 4 and 6 months of age was associated with non-allergic asthma. (7b)
» Usage of paracetamol during pregnancy and during the early months of life may play a role in the development of allergic and non-allergic asthma in children. However, due to obvious ethical reasons, direct evidence for this association (i.e. a double-blind, prospective study) is not available. (7b)
» A mat ched pat i ent - si bl i ng st udy on t he usage of paracet amol and t he subsequent devel opment of al l ergy and ast hma.
» A summary of significant findings in the study
» Source: Koniman, R.; Chan, Y. H.; Tan, T. N.; Van Bever, H. P., (2007). A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma. Pediatric Allergy And Immunology: Official Publication Of The European Society Of Pediatric Allergy And Immunology, 18 (2), pp. 128-34. . Retrieved on February 3, 2011, from Medline database.
Differences between cases &
controls
Risk factors Comparison pair Outcome
of interest
n p-
value
Responses n %
Paracetamol
during
pregnancy
Allergic asthma cases vs.
non-allergic controls
(healthy siblings)
Allergic
asthma
19 0.03 Yes/no 6/17
vs.
0/17
35 vs. 0
Paracetamol in
first 6 months
of life
Allergic asthma cases vs.
non-asthma
controls (allergic & non-
allergic siblings)
Asthma 33 0.008 Yes/no 8/28
vs.
0/28
29 vs. 0
» Research:
» Study by Themsen and colleagues (2008) address a
possible association between intake of paracetamol
and risk of adult-onset asthma. A multidisciplinary
postal questionnaire survey concerning health and
lifestyle were used to prospectively study 19,349 adult
twins enrolled in the nationwide Danish Twin Registry.
» Finding:
» There was a higher prevalence of new-onset asthma
in subjects who reported frequent intake of
paracetamol at baseline compared with subjects
without this determinant (9).
»Conclusion:
» There is now substantive evidence that the risk of
asthma may be increased by exposure to paracetamol
» in the intrauterine environment, in infancy, later
childhood and in adult life (Farquhar et al., 2009)
» Further research is urgently required, in particular
Randomized Controlled Trials into the long-term
effects of frequent paracetamol use in childhood, to
determine the magnitude and characteristics of any
such risk (Farquhar et al., 2009)
Ref erences » 1. Aki nbami , L. J., Moorman, J. E., and Liu X.
( 2011). Asthma Prevalence, Health Care Use, and
Mortality: United States, 2005 – 2009. Nat i onal Heal t h St at i st i cs
Report s No. 32. January 12 2011. Ret r i eved f rom
ht t p: / / www. cdc. gov/ nchs/ dat a/ nhsr/ nhsr 032. pdf
» 2. Beasl ey, R. , Cl ayt on, T. , Crane, J. , von Mut i us, E. ,
Lai C. K. , Mont ef ort , S. , and St ewart , A.
( 2008) . Associ at i on bet ween paracet amol use i n i nf ancy
and chi l dhood, and r i sk of ast hma,
rhi noconj unct i vi t i s, and eczema i n chi l dren aged 6- 7
years: anal ysi s f rom Phase Three of t he ISAAC programme.
Lancet 372 ( 9643) , pp. 1039- 48. Ret r i eved February 3, 2011, f rom
Medl i ne Dat abase.
» 3. CDC ( 2011) Fast St at s: Ast hma. Ret r i eved f rom
ht t p: / / www. cdc. gov/ nchs/ FASTATS/ ast hma. ht m
» References cont.
» 4. CDC (2011). Asthma: Data and Surveillance. Retrieved from http://www.cdc.gov/asthma/asthmadata.htm
» 5. CDC (2011). Asthma: Management and Treatment. Retrieved from http://www.cdc.gov/asthma/management.html
» Center for Disease Control and Prevention’s (CDC) National Asthma Control Program (2011). Asthma Fast Facts. Retrieved from http://www.cdc.gov/asthma/pdfs/asthma_fast_facts_statistics.pdf
» 6. Farquhar, H., Stewart, A., Mitchell, E., Crane, J., Eyers, S., Weatherall, M., and Beasley, R. (2010). The role of paracetamol in the pathogenesis of asthma. Clinical & Experimental Allergy, 40 (1), p32-41. Retrieved on February 3, 2011, from Health Source: Nursing/Academic Edition database.
» Ref erences cont .
» 7. Moorman, J. E. , Rudd, R. A. , Johnson, C. A. , Ki ng, K. , Mi nor, P. , Bai l ey, B. , Scal i a, M. R. , and Aki nbami , L. J. ( 2007).
National Surveillance for Asthma --- United States, 1980—2004.
MMWR Survei l l ance Summari es, 56 ( SS08) ; 1- 14; 18- 54. Ret r i eved f rom
ht t p: / / www. cdc. gov/ mmwr/ previ ew/ mmwrht ml / ss5608a1. ht m
» 7b. Koni man, R. ; Chan, Y. H. ; Tan, T. N. ; Van Bever , H. P. , ( 2007) . A
mat ched pat i ent - si bl i ng st udy on t he usage of
paracet amol and t he subsequent devel opment of al l ergy
and ast hma. Pedi at r i c Al l ergy And
Immunol ogy: Of f i ci al Publ i cat i on Of The European Soci et y Of Ped
i at r i c Al l ergy And Immunol ogy, 18 ( 2) , pp. 128- 34. . Ret r i eved
on February 3, 2011, f rom Medl i ne dat abase.
» Ref erences cont .
» 8. Morr i s, M. J. , ( 2010) . Ast hma. Emedi ci ne. Ret r i eved f rom
ht t p: / / emedi ci ne. medscape. com/ art i cl e/ 296301- overvi ew
» Nat i onal Heart Lung and Bl ood Inst i t ut e Di seases and Condi t i ons
Index(NHLBI) ( 2011) . Ast hma. Ret r i eved From
ht t p: / / www. nhl bi . ni h. gov/ heal t h/ dci / Di seases/ Ast hma/ Ast hma_Wha
t Is. ht ml
» 9. Thomsen, S. F. , Kyvi k, K. O. , Skadhauge, L. , St ef f ensen, I. ,
and Backer, V. ( 2008) .
» Int ake of Paracet amol and Ri sk of Ast hma i n Adul t s. Journal
of Ast hma, 45 ( 8) , p675- 676, Ret r i eved f rom Heal t h Source:
Nursi ng/ Academi c Edi t i on dat abase.
» 10. Upt odat e ( 2011) . Acet ami nophen ( paracet amol ) : Drug i nf ormat i on.
Ret r i eved f rom
ht t p: / / www. upt odat e. com/ cont ent s/ acet ami nophen- paracet amol -
drug- i nf ormat i on?source=search_resul t &sel ect edTi t l e=1~150