Respiratory Disease And Lung Function

By Author: Ibrahim Machiwala
Total Articles: 463
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Rationale:
Oxidative stress may increase the risk of asthma, contribute to asthma progression, and decrease lung function. Previous research suggests that use of acetaminophen, which is hypothesized to reduce antioxidant capacity in the lung, is associated with an increased risk of asthma.
Hypothesis:
Acetaminophen use may also be associated with chronic obstructive pulmonary disease (COPD) and decreased lung function.

Objectives:
To investigate the associations between use of pain medication, particularly acetaminophen, and asthma, COPD, and FEV1 in adults.

Methods:
A cross-sectional analysis using the Third National Health and Nutrition Examination Survey.

Measurement and Main Results:
Increased use of acetaminophen had a positive, dose-dependent association with COPD (adjusted odds ratio for increasing category of intake, 1.16; 95% confidence interval [CI], 1.09-1.24; p value for trend < 0.001)
and an inverse association with lung function (daily user compared with never users, -54.0 ml; 95% CI, -90.3 to -17.7, adjusted).
We confirmed a dose-response ...
... association of acetaminophen use and asthma (adjusted odds ratio, 1.20; 95% CI, 1.12-1.28; p value for trend < 0.001).

Conclusions:
This study provides further evidence that use of acetaminophen is associated with an increased risk of asthma and COPD, and with decreased lung function.

Methods:
This research was conducted using data from the Third National Health and Nutrition Examination Survey (NHANES III),
which is a cross-sectional survey of the U.S. noninstitutionalized population conducted between 1988 and 1994.
Included in this analysis are all participants aged between 20 and 80 years, with complete data for relevant exposures, outcomes, and confounding factors.

Data Collection:
Questionnaire data were collected by trained interviewers who gathered information on race/ethnicity, medical history, socioeconomic status, use of medication, and smoking history.
Participants were also asked whether they had taken any of the following pain medications in the last month and, if so, how often they had used each:
aspirin (including Anacin, Bufferin, Ecotrin, Ascriptin, or Midol), acetaminophen (including Tylenol, Anacin-3), and ibuprofen (including Advil, Nuprin, Medipren).

Participants attended a mobile examination unit where all physical measurements were taken, including height and weight.
Lung function tests were completed, providing data on FEV1 and FVC. Skin-prick testing using the prick-puncture technique was performed with 10 allergens

Statistical Analyses:
Using self-reported smoking history, participants were classified as
never smokers, ex-smokers, and current smokers
lifetime cigarette consumption was quantified in pack-years.

? Before analyses, analgesic use was arbitrarily divided into categories comprising
1. never users,
2. occasional users (1-5 times in the past month),
3. regular users (6-29 times in the past month), and
4. daily users (> 29 times in the past month).

Asthma was defined as self-report of ever having physician-diagnosed asthma.
COPD was defined as self-reported physician-diagnosed emphysema and/or chronic bronchitis, or by Global Initiative for Chronic Obstructive Lung Disease spirometry criteria (FEV1/FVC < 70% and FEV1 < 80% where percent-predicted pulmonary function was calculated using established reference values
Individuals were defined as allergen skin-test positive if the mean wheal diameter of any allergen response was at least 3 mm greater than the mean saline response.
The association between use of analgesics and lung disease or allergic sensitization was analyzed using multiple logistic regression, with analgesics initially modeled as set of categoric variables, and then as a trend using a single, ordered categoric variable, where appropriate.
We sought to establish whether any association of asthma with acetaminophen use was from systematic avoidance of nonsteroidal antiinflammatory drugs, particularly aspirin, by examining the dose-response effect of acetaminophen in those who used and did not use aspirin.
The relation between use of analgesics in the last month and FEV1, adjusted for age, sex, height, smoking (status and pack-years), and race/ethnicity, was explored using linear regression.
All regression analyses were investigated for possible interactions between exposure and confounding factors, particularly sex, age, smoking, and antioxidant intake.

Results:
The demographics and other characteristics were similar in subjects included in the study compared with those excluded because of missing data, with the exception that excluded participants were slightly older.
Demographic Results Table 1
Among study participants, the prevalence of asthma and COPD were 6.9 and 11.8%, respectively, and 2.8% had both respiratory diseases.
About 4% of participants were daily users of acetaminophen as compared with 8.2 and 2.5% for aspirin and ibuprofen, respectively.
Approximately 3% of the population reported use of all three pain medications in the last month
An increased use of acetaminophen was associated with an increased prevalence of asthma in a dose-dependent manner.
The odds ratio (OR) for increasing category of intake was 1.20 (95% confidence interval [CI], 1.12-1.28; p value for trend < 0.001; Table 2).
Next, we considered whether this was a specific association or whether all types of pain medications might be used more often by people with asthma.
Neither the use of aspirin nor the use of ibuprofen was associated with the prevalence of asthma.
When the outcome was restricted to current asthma, the results were unchanged (OR trend, 1.20; 95% CI, 1.11-1.29; p value for trend < 0.001), and the results were similar for different levels of asthma severity.
They also examined
acetamenophen & atopic asthma association(p value for interaction, 0.09, OR for trend, 1.02; 95% CI, 0.85-1.21)
No association
Where as there was a significant association for acetaminophen use and nonatopic asthma (OR for trend, 1.41; 95% CI, 1.06-1.86).
Acetaminophen use was also associated with an increased prevalence of COPD (OR for increasing category of intake, 1.16; 95% CI, 1.09-1.24; p value for trend < 0.001; Table 3).
Excluding subjects with asthma from the analysis had little or no effect on the magnitude of the acetaminophen-COPD association (OR for increasing category of intake, 1.15; 95% CI, 1.07-1.25; p value for trend < 0.001).
when COPD was defined by self-reported physician diagnosis only (current bronchitis and emphysema), or by objective lung function criteria only (GOLD stage 2 to indicate presence of disease), the adjusted ORs (for trend, taking acetaminophen as an ordered categoric variable) were 1.24 (95% CI, 1.13-1.37) and 1.15 (95% CI, 1.06-1.25), respectively.
FEV1 levels were inversely associated with acetaminophen use, and the association was nonlinear (Table 4).

Discussion:
The current study results are consistent with previous research demonstrating a positive association between acetaminophen use and prevalence of asthma.

1.Shaheen SO, Sterne JA, Songhurst CE, Burney PG. Frequent paracetamol use and asthma in adults. Thorax 2000;55:266-270

2.Newson RB, Shaheen SO, Chinn S, Burney PG. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J 2000;16:817-823

3.Shaheen SO, Newson RB, Sherriff A, Henderson AJ, Heron JE, Burney PG, Golding J. Paracetamol use in pregnancy and wheezing in early childhood. Thorax 2002;57:958-963

4.Barr RG, Wentowski CC, Curhan GC, Somers SC, Stampfer MJ, Schwartz J, Speizer FE, Camargo CA Jr. Prospective study of acetaminophen use and newly diagnosed asthma among women. Am J Respir Crit Care Med 2004;169:836-841.

We also investigated the relation of acetaminophen with the prevalence of COPD and found a significant dose-response relation, which was of about the same magnitude as the association for asthma.
Increased use of acetaminophen also was associated with decreased lung function, although this effect was seen only in participants reporting daily (or greater) use of acetaminophen.
Finally, we found that regular use of ibuprofen was associated with higher lung function

Strengths:
One strength of this study is the use of the NHANES III data, Participants were unaware of the study hypothesis at the time of data collection, thus eliminating potential response bias in answering the pain medication questions.
In addition, the use of lung function data provided an objective assessment of respiratory health

Limitations:
The cross-sectional design of the study
The result may be explained by uncontrolled confounding or by the tendency for persons with disease to use more analgesics (i.e., reverse causality).
incomplete characterization of the exposure
In this study, we assumed that reported use in the prior month is representative of long-term use.

Biostatistics:
Measures of strength of association
A popular measure of the strength of an association b/w 2 variables is relative risk(R.R)
Widely used in research by clinicians & epidemiologists
Defined as
the ratio of incidence rate for persons exposed to a risk factor to the incidence rate for those not exposed to a risk factor
RR=[incidence rate among exposed/incidence rate unexposed]
Table 2/2

Odds Ratio:
Another commonly used measure of strength of association
Sometimes called relative
Odds has received wide use in case control studies
Defined as the ratio b/w a/b to c/d
Valid measure of strength of association

Cross Sectional Surveys:
Aim at quantifying the distribution of certain variables in a study population at a point of time.
Quantify the burden of disease/in a given population and are useful for hypothesis generation
Cross sectional surveys cover a sample of the population.If a cross sectional study covers the whole population it is called a census

Correlational Techniques:
Correlation: used to establish & quantify the strength and direction of the relationship b/w 2 variables
Regression : used to express the functional relationship b/w 2 variables,so that the value of one variable can be predicted from the knowledge of the other.