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