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Caffeine and airway resistance

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Title:
Caffeine and airway resistance
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English
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Crump, Gwyn N
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University of South Florida
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Subjects / Keywords:
IOS
methylxanthine
pulmonary
spirometry
impulse
oscillometry
Dissertations, Academic -- Public Health -- Masters -- USF   ( lcsh )
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government publication (state, provincial, terriorial, dependent)   ( marcgt )
bibliography   ( marcgt )
theses   ( marcgt )
non-fiction   ( marcgt )

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Summary:
ABSTRACT: This study investigated the effect of caffeine on airway resistance. The subjects were drawn from volunteers (18-90 years old) in good health, with no major cardiopulmonary conditions. We found no association between the consumption of a single cup of the caffeinated beverage coffee and a decrease in airway resistance within one hour in a normal sample of subjects as measured by impulse oscillometry nor with conventional spirometry . It appears that any possible bronchodilatory effect of the caffeine from a single cup of coffee in a normal population is below the limit of detection of spirometry and impulse oscillometry or is not sufficiently expressed in the one hour time frame of the study. The study did validate currently accepted methods of using the Jaeger impulse oscillometry (IOS) measurement for use at the University of South Florida (USF). The impulse oscillometry technique was found to be a useful adjunct to conventional pulmonary function testing.Conventional pulmonary function testing provides a useful measure of a person's ability to breathe yet is difficult to perform and only indirectly guides the physician to the diagnosis of the pathology behind the person's breathing difficulties. The impulse oscillometry technique may help the physician to noninvasively determine the location of a pulmonary obstruction by measurement of the dynamics of sound wave travel through the airways of the lungs.
Thesis:
Thesis (M.S.P.H.)--University of South Florida, 2004.
Bibliography:
Includes bibliographical references.
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by Gwyn N. Crump, M.D.
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Title from PDF of title page.
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Document formatted into pages; contains 82 pages.

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oclc - 57723533
notis - AJU6741
usfldc doi - E14-SFE0000559
usfldc handle - e14.559
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Caffeine and Airway Resistance by Gwyn N. Crump, M.D. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Public Health Department of Environmental and Occupational Health College of Public Health University of South Florida Major Professor: Stuart Brooks, M.D. Robert Haight, M.D., M.S.P.H. Philip Roets, Sc.D. Date of Approval: November 16, 2004 Keywords: impulse, oscillometry, spirometry, IOS, pulmonary, methylxanthine Copyright 2004, Gwyn Crump, M.D.

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Dedication I would like to dedicate this work to my wife, Alice, who has encouraged me, stood beside me and inspired me in these efforts.

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Acknowledgements I would like to thank Dr. Robert Haight for his assistance in this project. I would also like to thank Dr. Stuart Brooks for providing me encouragement and the opportunity to work on this project.

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i Table of Contents List of Tables iii List of Figures iv Abstract v Introduction 1 Caffeine 1 Spirometry 2 Impulse Oscillometry 2 Asthma 4 Methods 6 Study Subjects 6 Data Collected 7 Pulmonary Measurement and Analysis 7 Results 11 Study Sample Characteristics 11 Impulse Oscillometry Measurements 14 Spirometric Measurements 14 Discussion 16 Conclusions 18 References 19

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ii Appendices 22 Appendix A: Questionnaires 23 Appendix B: Study Sample Characteristics 28 Appendix C: Age, Gender and Ethnicity Distributions 29 Appendix D: Health Characteristics and Exposures Distributions 32 Appendix E: Pre and Post Coffee Symptom Questionnaire Results 40 Appendix F: Pre and Post Coffee Symptom Questionnaire Distributions 41 Appendix G: Impulse Oscillometry Measurements 53 Appendix H: Spirometric Measurements 54 Appendix I: Respiratory Measurements Distributions 55 Appendix J: Analysis of Post-test vs Pre-test Differences in R5, R20 and FEV1 71

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iii List of Tables Table 1. Study Sample Characteristics 12 Table 2. Pre and Post Coffee Symptom Questionnaire Results 13 Table 3. Impulse Oscillometry Measurements 14 Table 4. Spirometric Measurements 15

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iv List of Figures Figure 1. Impulse Oscillometer 3 Figure 2. Use of Spirometry Equipment 8 Figure 3. IOS Restrictor Screen Door 9 Figure 4. IOS Subject Hand Position 9

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v Caffeine and Airway Resistance Gwyn N. Crump, MD ABSTRACT This study investigated the effect of caffeine on airway resistance. The subjects were drawn from volunteers (18-90 years old) in good health, with no major cardiopulmonary conditions. We found no association between the consumption of a single cup of the caffeinated beverage coffee and a decrease in airway resistance within one hour in a normal population of subjects as measured neither by impulse oscillometry nor with conventional spirometry. It appears that any possible bronchodilatory effect of the caffeine from a single cup of coffee in a normal population is below the limit of detection of spirometry and impulse oscillometry or is not sufficiently expressed in the one-hour time frame of the study. The study did validate currently accepted methods of using the Jaeger impulse oscillometry (IOS) measurement for use at the University of South Florida (USF). The impulse oscillometry technique was found to be a useful adjunct to conventional pulmonary function testing. Conventional pul monary function testing provides a useful measure of a person’s ability to breathe yet is difficult to perform and only indirectly guides the physician to the diagnosis of the pathology behind the person’s breathing

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vi difficulties. The impulse oscillometry technique may help the physician to noninvasively determine the location of a pulmonary obstruction by measurement of the dynamics of sound wave travel through the airways of the lungs.

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1 Introduction Caffeine Mankind has been drinking caffeinated beverages for almost 5000 years with the discovery of brewed tea attributed to th e Second Emperor of China, Shen Nung, also known as the divine healer. Tea and coffee contain about 20-60 mg and 125-185 mg of caffeine respectively per cup and have been prized throughout their history as both stimulants and palliatives for respiratory disorders1, 2. The efficacy of caffeine in asthma has been evaluated in a recent evidence based medicine review of clinical trials which concludes “Caffeine appears to improve airways modestly in people with asthma for up to four hours”3. Yet, still much is not known both about the mechanisms of action of caffeine and the extent to which the general population, consciously or unconsciously uses caffeine to self-medicate respiratory ailments. Caffeine and its more active metabolic products, theophylline and theobromine have long demonstrated bronchodilator effects through relaxation of bronchial smooth muscle4. They are phosphodiesterase (PDE) inhibitors and decrease the rate at which the intracellular second messengers cAMP and cGMP are degraded. Phosphodiesterase inhibitors also increase diaphragmatic contractility and respiratory drive probably through adenosine receptor antagonism5. Recently, theophylline has been shown to exercise immunomodulatory and anti-inflammatory

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2 properties even at sub-bronchodilator doses and plasma levels6. This has been confirmed by measurement of exhaled nitric oxide levels after caffeine consumption7. The discovery of tissue specific PDE isoenzymes in the 1970’s has led to interest in the development of selective PDE inhibitors such as roflumilast and cilomilast8, 9. Selective PDE4 inhibitors are hoped to offer improved anti-inflammatory effects and improved safety over nonspecific PDE inhibitors such as theophylline. The PDE4 specific inhibitors cilomilast and roflumilast are now in clinical trials and appear promising10-12. Spirometry Spirometry has great utility for the diagnosis of respiratory disorders, monitoring of pulmonary disease progression, and assessment of treatment efficacy. It is a composite measure of lung function that reveals much about overall air exchange capability yet is less illuminating of the various factors contributing to obstructive and restrictive lung deficits. These factors may include body habitus, chest wall elasticity, lung compliance, airway resistance, cystic air trapping, respiratory muscle weakness and CNS impairment13, 14. Thus for obstructive lung disorders it has been desirable to directly measure airway resistance and many techniques have been developed to accomplish this15. Unfortunately these methods of airway resistance measurement such as plethysmography and the forced oscillation technique have previously been unsuitable for clinical application due to complexity and cost. Impulse Oscillometry Recently an application of the forced oscillation technique known as impulse

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3 oscillometry (IOS) has become available in a compact package. This Jaeger Masterscreen IOS package is non-invasive and FDA approved for IOS and conventional spirometry measurements. A diagram of the typical equipment is shown in Figure 116. Figure 1. Impulse Oscillometer Mouthpiece Impulse oscillometry uses the pressure-flow relationship of artificial impulseshaped test signals produced by an external generator. These artificial signals are superimposed on the normal tidal breathing waveform of the subject while he is breathing ambient air. Fast Fourier Transform (FFT) and quotient calculation is performed to derive frequency versus impedance, resistance and reactance curves. This data can then be used to describe airflow characteristics of the subjects’ lungs both in degree of and location of impairment16. Useful respiratory impedance parameters include R5, total

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4 respiratory resistance; R20, proximal respiratory resistance; and X5, distal capacitive reactance (inversely related to the compliance of the lung). Asthma Asthma is the intermittent obstruction of lung airways in response to intrinsic or environmental provocation such as allergens, physiologic stress or infection. Asthma is thought to be under diagnosed both in the general population and the elderly. Many times there is a history of wheezing, especially after viral infections. Often childhood asthma enters remission in the second decade of life only to return in adulthood. Asthma may occur after decades of pulmonary insult from tobacco smoking, occasionally secondary to workplace exposures, and sometimes explosively with no prior history of asthma17, 18. Reports on the use of over-the-counter bronchodilator medications in asthmatics indicate not only are asthmatics under diagnosed, but medically diagnosed asthmatics who self-treat are less likely to receive and use anti-inflammatory therapy19. Modern anti-inflammatory therapy can both relieve the symptoms of and delay the progression of asthma. Further reports of other self and alternative medicine treatments for asthma include herbal products, coffee, black tea, reflexology, acupuncture, massage therapy, homeopathy, aromatherapy, and spinal manipulation20-23. Treatments, such as Chinese herbs, may have concerning safety profiles and unpredictable interactions with conventional medications24. Even if these alternative therapies are partially efficacious, it may only delay the diagnosis of asthma until an episode of respiratory failure places the patient in a hospital emergency department.

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5 Asthma is not the only cause of obstructive pulmonary pathology. Other obstructive lung pathologies include chronic obstructive lung disease (chronic bronchitis or emphysema), bronchiectasis, cystic fibrosis, and bronchiolitis25. Recently it has been recognized that vocal cord dysfunction may present with asthma-like symptoms26. Each of these illnesses tends to obstruct different areas of the respiratory tree. Asthma tends to exercise a predominant effect on the bronchi (larger airways) while chronic obstructive lung disease tends to affect both large and small airways. In bronchiectasis, there is dilatation of the bronchi with obstruction of the smaller distal airways. Cystic fibrosis tends to initially affect the smaller airways with later evolution to bronchiectasis. In contrast, bronchiolitis tends to affect the bronchioles (smaller airways). Vocal cord dysfunction affects the flow of air through the larynx (voicebox).

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6 Methods The study was designed to investigate the question: “Is there a significant bronchodilator effect observed in a normal population with the consumption of a single cup of caffeinated coffee?” The hypotheses to be tested was: “A bronchodilator effect as measured as total respiratory resistance at 5 Hz by impulse oscillometry will be observed in a normal population with the consumption of a single cup of caffeinated coffee after one hour.” Study Subjects Subjects by interview had no history of diagnosis of major cardiopulmonary conditions. The sample consisted of 20 subjects with an approximately equal distribution of gender in the group. Subjects had to be of a certain age group to be eligible for the study: ages 18 to 90 years old (dates of birth 1914-1986). If the subj ects were of this age group and decided to participate in this study, each reviewed the informed consent and discussed the study and possible participation with the study physician. If a subject was interested in participating, the informed consent was be signed before any study-related test or procedure was done. After signing the informed consent, screening tests were completed to determine if a subject met the requirements to be in the study.

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7 Potential candidates were screened to determine whether they could be considered “normal”. Screening tests include completing standard questionnaires, undergoing a physician’s interview, submitting to a physical examination and completing spirometry measurements. The questionnaires are shown in Appendix A. The study physician investigator reviewed the questionnaire responses; interviewed the subjects and completed spirometry. All spirometry was performed according to American Thoracic Society specifications and predicted values were taken from Hankinson, Crapo and coworkers values27. In order to qualify, participants must have recorded a negative questionnaire response suggestive of heart problems such as chest pain, irregular heartbeats or uncontrolled high blood pressure. They also must not have been receiving any medical treatment for any pulmonary condition. Data Collected Data was collected about the airway resistance of subjects using the Jaeger impulse oscillometer and conventional pulmonary function tests. These tests were performed before and 60 minutes after coffee consumption and subjects were interviewed as to current and previous state of health, smoki ng history and current respiratory symptoms. Patients were interviewed before and after the test, filled out the questionnaires in Appendix A and asked to report any respiratory or sensory changes. Pulmonary Measurement and Analysis This study was performed in the respiratory investigations lab of the Occupational and Environmental Medicine Department at the College of Public Health at the University of South Florida, Tampa, FL. Over a two-week period, twenty subjects were

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8 interviewed and tested during a single one to two hour visit. With the exception of the informed consent form, all documentation was only identified by subject number. They filled out a questionnaire screening for major medical conditions, underwent an interview and received a screening exam. They then filled out a pre-test symptom questionnaire, performed conventional spirometry and underwent impulse oscillometry. Spirometry and impulse oscillometry were perfomed in a seated position for safety. The subject was fitted with a nose clip and instructed in the performance of the forced expiratory maneuver. The use of the spirometry equipment is illustrated in Figure 2. Three acceptable maneuvers were obtained and the best was retained for comparison. Figure 2. Use of Spirometry Equipment The restrictor screen door (Figure 3a) on the impulse oscillometer was closed (Figure 3b) and the subject instructed on the IOS procedures. The device was zeroed and the subject was then instructed to begin breathing through the mouthpiece while supporting his cheeks with his hands (Figure 4). After thirty seconds of breathing

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9 normally through the mouthpiece and acclimating to the device, thirty seconds of measurements were taken. Figure 3. IOS Restrictor Screen Door Figure 4. IOS Subject Hand Position

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10 The subjects then received one eight ounce cup of premium caffeinated coffee and filled out a medical history questionnaire. The coffee was the brand name Starbucks Breakfast Blend and was prepared according to the instructions received with the package of coffee. One tablespoon (15 milliliters of dried ground coffee) per six ounces (180 milliliters) of water was prepared using a drip type coffee maker. One hour later the subjects again filled out a symptom questionnaire, performed conventional spirometry and underwent impulse oscillometry. These questionnaires are shown in Appendix A. The investigator then interviewed the subject and performed a post-test auscultation of the subject’s chest to conclude the subject’s visit. Jaeger impulse oscillometry and conventional spirometry data were collected using the Jaeger LabManager software. It was then was integrated with medical history data in a Microsoft Excel spreadsheet and analyzed using the JMP 5.1 statistical program.

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11 Results Study Sample Characteristics The study sample of twenty subjects was split approximately equally between male(11) and female(9) subjects. The age of the sample ranged from 26 to 68 years with a median age of 40 years. Seventeen of the subjects were Caucasian, two were USAsian, and one was US-African. Sixteen of the twenty subjects reported no health problems. Health problems that were reported included mitral valve prolapse, migraine headaches, lower back pain, glaucoma, urinar y stones, history of fractures, hypertension, and frequent urinary tract infections. Pre and post coffee consumption symptoms were monitored by use of the questionnaires in Appendix A. Subjects were asked to describe symptoms of heavy or difficulty in breathing, phlegm production, runny or irritated nasal passages, throat irritation or burning, sensation of weight or tightness of the chest and feeling of chest burning. Each symptom was rated a numeric scale of none(1), very little(2), moderate amount(3) and very much(4). Descriptive statistics for the study sample are shown in Table 2 and Appendices E and F. Additional sample characterstics are detailed in Table 1 and Appendices B, C and D.

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12 Table 1. Study Sample Characteristics Gender Female (9) 45% Male (11) 55% Race / Ethnicity Caucasian (17) 85% US African (1) 5% US Asian (2) 10% Age Range 26-68 years Median 40 years Mean 41.15 years Standard Deviation 9.76 years Health Problems None (16) 80%, Mitral valve prolapse (1) 5%, Migraine headaches (1) 5%, Lower back pain (1) 5%, Glaucoma (1) 5%, Urinary stones (1) 5%, History of fractures (1) 5%, Hypertension (1) 5%, Frequent urinary tract infections (1) 5% Medications None (10) 50%, Multivitamin (3) 15%, Calcium (1) 5%, Vitamin C (1) 5%, Saw palmetto (1) 5%, Lo Ovral (1) 5%, Tryoptic (1) 5%, Naprosyn (1) 5%, Premarin (1) 5%, OTC sinus medication (1) 5%, Yasmin (1) 5%, Spector (1) 5%, Paxil (1) 5% Tobacco Smoker No (15) 75% Yes (3) 15% Past (2) 10%

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13 Table 2. Pre and Post Coffee Symptom Questionnaire Results Median Mean Standard Deviation Pre Coffee 1.000 1.150 0.489 Breathing Difficulties Post Coffee 1.000 1.100 0.447 Pre Coffee 1.000 1.350 0.671 Phlegm Production Post Coffee 1.000 1.450 0.605 Pre Coffee 1.000 1.200 0.523 Nasal Problems Post Coffee 1.000 1.100 0.308 Pre Coffee 1.000 1.200 0.523 Throat Irritation Post Coffee 1.000 1.200 0.523 Pre Coffee 1.000 1.150 0.366 Chest Tightness Post Coffee 1.000 1.050 0.224 Pre Coffee 1.000 1.000 0.000 Chest Burning Post Coffee 1.000 1.000 0.000

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14 Impulse Oscillometry Measurements A significant trend could not be detected in impulse oscillometry measurements. The sample measurements appeared to be normally distributed and were analyzed using a matched pairs t-test. The results are summarized in Table 3 and detailed in Appendices G, I and J. Mean pre-coffee total respiratory resistance at 5 Hz (R5) was 4.125. Mean post-coffee R5 was 4.107. The t value was -0.15236 and the probability of obtaining this t value through chance alone when there is no difference is 0.4403. Therefore the null hypothesis failed to be rejected at alpha= 0.05. Wilcoxon Sign-Rank test results were similar. Table 3. Impulse Oscillometry Measurements Median Mean Standard Deviation Pre-coffee R5 4.000 4.125 1.095 Post-coffee R5 3.865 4.107 1.247 Spirometric Measurements A significant trend could not be detected in conventional spirometry measurements of forced expiratory ventilation in one second (FEV1). The sample measurements did not appear to be normally distributed and therefore were analyzed using a matched pairs Wilcoxon Sign-Rank test. The results are summarized in Table 4 and detailed in Appendices H, I and J. Median pre-coffee FEV1 was 3.430. Median post-coffee FEV1 was 3.545. The Wilcoxon Sign-Rank test value was 7.000 and the probability of obtaining this value through chance alone when there is no difference is

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15 0.387. Therefore this secondary measure also failed reach significance at alpha= 0.05. Matched pairs t-test results were similar. Table 4. Spirometric Measurements Median Mean Standard Deviation Pre-coffee FEV1 3.430 3.425 0.842 Post-coffee FEV1 3.545 3.454 0.832

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16 Discussion This study compared respiratory parameters in a sample of normal subjects before and one hour after consumption of one cup of the caffeinated beverage coffee. Although the study failed to show a significant difference in R5 before and after consumption of this beverage it did provide useful experience in the use of the Jaeger Impulse Oscillometer. Further, this study failed to confirm a bronchodilator effect in normal individuals from consumption of caffeine as measured by changes in FEV1. This stands in contrast to previous studies on asthmatics in which an increase in FEV1 was measured. One possibility for the minimal changes observed in the study was that the study sample was too healthy. Previous studies th at demonstrated a bronchodilator effect were performed on asthmatics. This study excluded known asthmatics. Another explanation was that the interval of one hour between consumption of the coffee and measurement of lung parameters was too short to allow time for a significant bronchodilator effect to develop. Some studies in asthmatics demonstrated a larger effect in intervals of two to four hours. It is po ssible that there is a measurable effect in a normal population but it takes longer than one hour to develop. It is also possible that the dose of caffeine delivered by this coffee was less than that delivered by other brands or types of coffee. No attempt was made to quantify the caffeine content of this coffee. Alt hough Starbucks Breakfast Blend Coffee was

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17 presumed to have between 125 and 185 mg of caffeine per cup the actual caffeine content of this blend is unknown to this researcher. Caffeine has complex pharmacodynamics and remains in the body for more than one day. Thus in a habitual coffee drinker the effect may be masked by the previous days consumption of coffee. There may simply be too much intra-subject and inter-subject variability in the in the amount of bronchodilation and bronchoconstriction existing even in normal subjects in response to environmental stimuli and personal characteristics from day to day and hour to hour. This “noise” would tend to mask small effects. This study could be repeated on asthmatic subjects to characterize their response to caffeine using the IOS. The caffeine dose given could be exactly determined and subjects could be asked to abstain from caffeine for more than just overnight. Finally the study could be performed over a longer period of time on normal subjects to determine when a bronchodilatory effect occurs in normal subjects. The study could be repeated with a greater attempt to control subjects activity and confounding exposures in the interval between the pre and post caffeine pulmonary measurements. The subjects were allowed to leave the lab area in the interval between being given the coffee and the post coffee respiratory measurements. By requiring the test subjects to remain in the lab area during the entire duration of the study the activities of the subjects can be monitored and external exposures could be controlled.

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18 Conclusions There was no evidence of bronchodilation induced one hour after consumption of a single cup of caffeinated coffee in normal individuals neither as measured by impulse oscillometry nor by conventional spirometry.

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19 References 1. Scott A, Beckwith S. In pursuit of tea. In Pursuit of Tea [webpage]. Available at: www.inpursuitoftea.com 2004. 2. Anonymous. The history of coffee. The Roast and Post Coffee Company [webpage]. Available at: www.realcoffee.co.uk 2004. 3. Bara AI, Barley EA. Caffeine for asthma.[update in Cochrane Database Syst Rev. 2001;(4):CD001112; PMID: 11687099]. Cochrane Database of Systematic Reviews. 2000(2):CD001112. 4. Macht DI, Ting G-C. A study of anti-spasmodic drugs on the bronchus. Journal of Pharmacology & Experimental Therapeutics. December, 1921 1921;18(5):373398. 5. Jenne JW. Bronchodilators. In: O'Byrne PM, Thomson NC, eds. Manual of Asthma Management London, England: W. B. Saunders Company Ltd.; 1995:291-320. 6. Banner KH, Spina D, Page CP. Drugs that reduce airways inflammation. In: Page CP, Banner KH, Spina D, eds. Cellular Mechanisms in Airways Inflammation Basel, Switzerland: Birkhauser Verlag; 2000:303-325. 7. Bruce C, Yates DH, Thomas PS. Caffeine decreases exhaled nitric oxide.[see comment]. Thorax. 2002;57(4):361-363. 8. Essayan DM. Cyclic nucleotide phosphodiesterases. Journal of Allergy & Clinical Immunology. 2001;108(5):671-680. 9. Spina D. Theophylline and PDE4 inhibitors in asthma. Current Opinion in Pulmonary Medicine. 2003;9(1):57-64. 10. Grootendorst DC, Gauw SA, Baan R, et al. Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease? Pulmonary Pharmacology & Therapeutics. 2003;16(2):115-120. 11. Profita M, Chiappara G, Mirabella F, et al. Effect of cilomilast (Ariflo) on TNF-

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20 alpha, IL-8, and GM-CSF release by airway cells of patients with COPD. Thorax. 2003;58(7):573-579. 12. Sturton G, Fitzgerald M. Phosphodiesterase 4 inhibitors for the treatment of COPD. Chest. 2002;121(5 Suppl):192S-196S. 13. Nava S, Rubini F. Lung and chest wall mechanics in ventilated patients with end stage idiopathic pulmonary fibrosis. Thorax. 1999;54(5):390-395. 14. Eissa NT, Ranieri VM, Corbeil C, et al. Analysis of behavior of the respiratory system in ARDS patients: effects of flow, volume, and time. Journal of Applied Physiology. 1991;70(6):2719-2729. 15. Klug B, Bisgaard H. Specific airway re sistance, interrupter resistance, and respiratory impedance in healthy children aged 2-7 years. Pediatric Pulmonology. 1998;25(5):322-331. 16. Anonymous. IOS User Manual, Version 4.5 Hoechberg, Germany: Erich Jaeger GmbH. 17. Zacharisen MC. Occupational asthma. Medical Clinics of North America. 2002;86(5):951-971. 18. Braman SS. Asthma in the elderly. Clinics in Geriatric Medicine. 2003;19(1):5775. 19. Kuschner WG, Hankinson TC, Wong HH, Blanc PD. Nonprescription bronchodilator medication use in asthma.[see comment]. Chest. 1997;112(4):987993. 20. Blanc PD, Kuschner WG, Katz PP, Smith S, Yelin EH. Use of herbal products, coffee or black tea, and over-the-counter medications as self-treatments among adults with asthma.[see comment]. Journal of Allergy & Clinical Immunology. 1997;100(6 Pt 1):789-791. 21. Blanc PD, Kuschner WG, Katz PP, Yelin EH. Reanalysis of Blanc PD et al, "Use of herbal products, coffee or black tea, and over-the-counter medications as self treatments among adults with asthma".[comment]. Journal of Allergy & Clinical Immunology. 2000;106(1 Pt 1):196. 22. Blanc PD, Trupin L, Earnest G, Katz PP, Yelin EH, Eisner MD. Alternative

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21 therapies among adults with a reported diagnosis of asthma or rhinosinusitis : data from a population-based survey.[see comment]. Chest. 2001;120(5):1461-1467. 23. Ernst E. Complementary/alternative medicine for asthma: we do not know what we need to know.[see comment]. Chest. 1999;115(1):1-3. 24. Ernst E. "Alternative" therapies for asthma : reason for concern?[comment]. Chest. 2001;120(5):1433-1434. 25. Weinberger SE, Drazen JM. Disturbances of Respiratory Function. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's Principles of Internal Medicine 15th ed. New York: McGraw-Hill; 2001:14461453. 26. McFadden ER, Jr., Zawadski DK. Vocal cord dysfunction masquerading as exercise-induced asthma. a physiologic cause for "choking" during athletic activities. American Journal of Respiratory & Critical Care Medicine. 1996;153(3):942-947. 27. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population.[see comment]. American Journal of Respiratory & Critical Care Medicine. 1999;159(1):179-187.

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22 Appendices

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23 Appendix A: Questionnaires Subject number:_______ Caffeine and Airway Resistance Study Pre-Coffee Questionnaire Today’s Date _______________________________________ People who are pregnant or have heart problems such as chest pain, irregular heartbeats or uncontrolled high blood pressure should not drink caffeinated beverages such as coffee. Do you have any health problems that would prevent you from drinking coffee or have you been told by a doctor, nurse or other healthcare provider that you should avoid caffeinated beverages such as coffee? Please circle “yes” or “no”. YES or NO Do you take any medications from a doctor or other healthcare provider for your lungs? Please circle “yes” or “no”. YES or NO

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24 Appendix A: (Continued) SUBJECT NUMBER: ___________________________________________ Pre-Coffee Consumption Symptom Questionnaire “At this point in time, to what degree do you note the following symptoms?” (1) Heavy or difficulty in your breathing 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (2) Phlegm production 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (3) Runny or irritated nose or nasal passages 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (4) Throat irritation or burning sensation 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (5) Sensation of a “weight” or tightness of the chest 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (6) Feeling of chest burning 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH

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25 Appendix A: (Continued) SUBJECT NUMBER: ___________________________________________ Post-Coffee Consumption Symptom Questionnaire “At this point in time, to what degree do you note the following symptoms?” (1) Heavy or difficulty in your breathing 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (2) Phlegm production 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (3) Runny or irritated nose or nasal passages 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (4) Throat irritation or burning sensation 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (5) Sensation of a “weight” or tightness of the chest 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH (6) Feeling of chest burning 1. NONE 2. VERY LITTLE 3. MODERATE AMOUNT 4. VERY MUCH

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26 Appendix A: (Continued) Subject number:_______ Caffeine and Airway Resistance Study Questionnaire Today’s Date _______________________________________ Gender: Male Female (circle one) 1) How old are you? ______________years 2) Do you have any health problems that you see a physician for? Please list them below. 1._________________________________________________________ 2. ________________________________________________________ 3. ________________________________________________________ 4. ________________________________________________________ 5.________________________________________________________ 3) Are you taking any medications? If so please list them below. (Including over the counter medications) 1._________________________________________________________ 2. ________________________________________________________ 3. ________________________________________________________ 4. ________________________________________________________ 5.________________________________________________________

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27 Appendix A: (Continued) 4) If you have ever smoked, answer the following. How many packs per day did you smoke? ________________________ For how many years did you smoke? ____________________________ When did you stop smoking? __________________________________ 5) On what date were you last ill? _________________________________________ 6) What illness did you have? ____________________________________________ 7) What is your occupation? _____________________________________________ 8) Are you exposed to second hand smoke at home or at work? Please circle “yes” or “no”. YES or NO 9) Were you or are you exposed to any gases, dusts, or fumes at your job? YES or NO If so, please explain: ____________________________________________ _____________________________________________________________________ 10) Do you ever wheeze or become short of breath? Please circle “yes” or “no”. YES or NO

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28 Appendix B: Study Sample Characteristics Gender Ethnicity Age Health Problems Medications Smoker Pack-years Male Caucasian 36 None None Past 1 Female US-Asian 37 None MVI, calcium No 0 Female Caucasian 26 None MVI No 0 Female US-Asian 35 None None No 0 Male Caucasian 39 None None No 0 Female Caucasian 48 None MVI, vitamin C No 0 Male Caucasian 35 None None No 0 Male Caucasian 36 None Saw palmetto No 0 Female Caucasian 40 MVP, migraine, LBP Lo Ovral Yes 15 Male Caucasian 42 None None Yes 0.1 Female Caucasian 42 None None No 0 Male Caucasian 42 Glaucoma, stones, fxTryoptic, naprosyn No 0 Female Caucasian 54 None Premarin, OTC sinusNo 0 Male Caucasian 45 None None No 0 Female Caucasian 26 None Yasmin Past 0.5 Male Caucasian 68 None Spector No 0 Male Caucasian 32 None None No 0 Male Caucasian 52 Hypertension None No 0 Female Caucasian 48 Frequent UTIs Paxil Yes 8 Male US-African 40 None None No 0

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29 Appendix C: Age, Gender and Ethnicity Distributions Distributions Gender Female Male Frequencies Level Count Prob Female 9 0.45000 Male 11 0.55000 Total 20 1.00000 N Missing 0 2 Levels

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30 Appendix C: (Continued) Ethnicity Caucasian US-African US-Asian Frequencies Level Count Prob Caucasian 17 0.85000 US-African 1 0.05000 US-Asian 2 0.10000 Total 20 1.00000 N Missing 0 3 Levels

PAGE 40

31 Appendix C: (Continued) Age 20 30 40 50 60 70 Quantiles 100.0% maximum 68.000 99.5% 68.000 97.5% 68.000 90.0% 53.800 75.0% quartile 47.250 50.0% median 40.000 25.0% quartile 35.250 10.0% 26.600 2.5% 26.000 0.5% 26.000 0.0% minimum 26.000 Moments Mean 41.15 Std Dev 9.7617675 Std Err Mean 2.1827976 upper 95% Mean 45.718648 lower 95% Mean 36.581352 N 20

PAGE 41

32 Appendix D: Health Characteristics and Exposures Distributions Health Problems Frequent UTIs Glacoma, stones, fx Hypertension MVP, migraine, LBP None Frequencies Level CountProb Frequent UTIs 10.05000 Glacoma, stones, fx 10.05000 Hypertension 10.05000 MVP, migraine, LBP 10.05000 None 160.80000 Total 201.00000 N Missing 0 5 Levels

PAGE 42

33 Appendix D: (Continued) Medications Lo Ovral MVI MVI, calcium MVI, vitamin C None Paxil Premarin, OTC sinus Saw palmetto Spector Tryoptic, naprosyn Yasmin Frequencies Level CountProb Lo Ovral 10.05000 MVI 10.05000 MVI, calcium 10.05000 MVI, vitamin C 10.05000 None 100.50000 Paxil 10.05000 Premarin, OTC sinus 10.05000 Saw palmetto 10.05000 Spector 10.05000 Tryoptic, naprosyn 10.05000 Yasmin 10.05000 Total 201.00000 N Missing 0 11 Levels

PAGE 43

34 Appendix D: (Continued) Smoker No Past Yes Frequencies Level Count Prob No 15 0.75000 Past 2 0.10000 Yes 3 0.15000 Total 20 1.00000 N Missing 0 3 Levels

PAGE 44

35 Appendix D: (Continued) Pack-years 0 5 10 15 Quantiles 100.0% maximum 15.000 99.5% 15.000 97.5% 15.000 90.0% 7.300 75.0% quartile 0.075 50.0% median 0.000 25.0% quartile 0.000 10.0% 0.000 2.5% 0.000 0.5% 0.000 0.0% minimum 0.000 Moments Mean 1.23 Std Dev 3.6992318 Std Err Mean 0.8271734 upper 95% Mean 2.9612938 lower 95% Mean -0.501294 N 20

PAGE 45

36 Appendix D: (Continued) Months Since Sick 0 5 10 15 20 25 Quantiles 100.0% maximum 24.000 99.5% 24.000 97.5% 24.000 90.0% 22.000 75.0% quartile 12.000 50.0% median 2.000 25.0% quartile 1.000 10.0% 0.750 2.5% 0.500 0.5% 0.500 0.0% minimum 0.500 Moments Mean 6.25 Std Dev 7.7577505 Std Err Mean 2.073346 upper 95% Mean 10.729192 lower 95% Mean 1.7708082 N 14

PAGE 46

37 Appendix D: (Continued) Occupation Case Mgr. City Planner Coast Guard Engineer Military Physician Rad. Clerk Reg. Nurse Secretary Student Frequencies Level Count Prob Case Mgr. 1 0.05000 City Planner 1 0.05000 Coast Guard 1 0.05000 Engineer 1 0.05000 Military 1 0.05000 Physician 9 0.45000 Rad. Clerk 1 0.05000 Reg. Nurse 2 0.10000 Secretary 2 0.10000 Student 1 0.05000 Total 20 1.00000 N Missing 0 10 Levels

PAGE 47

38 Appendix D: (Continued) Exposures None indirect tobacco workplace Frequencies Level CountProb None 160.80000 indirect tobacco 20.10000 workplace 20.10000 Total 201.00000 N Missing 0 3 Levels

PAGE 48

39 Appendix D: (Continued) Wheeze/SOB No Yes Frequencies Level Count Prob No 19 0.95000 Yes 1 0.05000 Total 20 1.00000 N Missing 0 2 Levels

PAGE 49

40 Appendix E: Pre and Post Coffee Symptom Questionnaire Results Pre Breathing Post BreathingPre Phlegm Post Phlegm Pre Nose Post Nose 1 1121 1 1 1121 1 1 1121 1 1 1321 1 1 1121 1 3 3332 2 1 1213 2 1 1111 1 2 1121 1 1 1111 1 1 1111 1 1 1111 1 1 1222 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1211 1 1 1111 1 Pre Throat Post Throat Pre TightnessPost Tightness Pre Burning Post Burning 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 3 3221 1 2 2211 1 1 1111 1 1 1211 1 1 1111 1 1 1111 1 2 2111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1 1 1111 1

PAGE 50

41 Appendix F: Pre and Post Coffee Symptom Questionnaire Distributions Distributions Pre Breathing 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 1.9000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.15 Std Dev 0.4893605 Std Err Mean 0.1094243 upper 95% Mean 1.3790278 lower 95% Mean 0.9209722 N 20

PAGE 51

42 Appendix F: (Continued) Post Breathing 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 1.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.1 Std Dev 0.4472136 Std Err Mean 0.1 upper 95% Mean 1.3093024 lower 95% Mean 0.8906976 N 20

PAGE 52

43 Appendix F: (Continued) Pre Phlegm 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 2.9000 75.0% quartile 1.7500 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.35 Std Dev 0.6708204 Std Err Mean 0.15 upper 95% Mean 1.6639536 lower 95% Mean 1.0360464 N 20

PAGE 53

44 Appendix F: (Continued) Post Phlegm 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 2.0000 75.0% quartile 2.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.45 Std Dev 0.6048053 Std Err Mean 0.1352386 upper 95% Mean 1.7330576 lower 95% Mean 1.1669424 N 20

PAGE 54

45 Appendix F: (Continued) Pre Nose 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 2.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.2 Std Dev 0.5231484 Std Err Mean 0.1169795 upper 95% Mean 1.444841 lower 95% Mean 0.955159 N 20

PAGE 55

46 Appendix F: (Continued) Post Nose 0.75 1 1.25 1.5 1.75 2 2.25 Quantiles 100.0% maximum 2.0000 99.5% 2.0000 97.5% 2.0000 90.0% 1.9000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.1 Std Dev 0.3077935 Std Err Mean 0.0688247 upper 95% Mean 1.2440518 lower 95% Mean 0.9559482 N 20

PAGE 56

47 Appendix F: (Continued) Pre Throat 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 2.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.2 Std Dev 0.5231484 Std Err Mean 0.1169795 upper 95% Mean 1.444841 lower 95% Mean 0.955159 N 20

PAGE 57

48 Appendix F: (Continued) Post Throat 0.5 1 1.5 2 2.5 3 3.5 Quantiles 100.0% maximum 3.0000 99.5% 3.0000 97.5% 3.0000 90.0% 2.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.2 Std Dev 0.5231484 Std Err Mean 0.1169795 upper 95% Mean 1.444841 lower 95% Mean 0.955159 N 20

PAGE 58

49 Appendix F: (Continued) Pre Tightness 0.75 1 1.25 1.5 1.75 2 2.25 Quantiles 100.0% maximum 2.0000 99.5% 2.0000 97.5% 2.0000 90.0% 2.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.15 Std Dev 0.3663475 Std Err Mean 0.0819178 upper 95% Mean 1.3214559 lower 95% Mean 0.9785441 N 20

PAGE 59

50 Appendix F: (Continued) Post Tightness 0.75 1 1.25 1.5 1.75 2 2.25 Quantiles 100.0% maximum 2.0000 99.5% 2.0000 97.5% 2.0000 90.0% 1.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1.05 Std Dev 0.2236068 Std Err Mean 0.05 upper 95% Mean 1.1546512 lower 95% Mean 0.9453488 N 20

PAGE 60

51 Appendix F: (Continued) Pre Burning 0.75 1 1.25 1.5 1.75 2 2.25 Quantiles 100.0% maximum 1.0000 99.5% 1.0000 97.5% 1.0000 90.0% 1.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1 Std Dev 0 Std Err Mean 0 upper 95% Mean 1 lower 95% Mean 1 N 20

PAGE 61

52 Appendix F: (Continued) Post Burning 0.75 1 1.25 1.5 1.75 2 2.25 Quantiles 100.0% maximum 1.0000 99.5% 1.0000 97.5% 1.0000 90.0% 1.0000 75.0% quartile 1.0000 50.0% median 1.0000 25.0% quartile 1.0000 10.0% 1.0000 2.5% 1.0000 0.5% 1.0000 0.0% minimum 1.0000 Moments Mean 1 Std Dev 0 Std Err Mean 0 upper 95% Mean 1 lower 95% Mean 1 N 20

PAGE 62

53 Appendix G: Impulse Oscillometry Measurements Pre R5 Pre R5 %ilePost R5 Post R5 %ileR5 ChangeR5 %ile Chg 3.85 138.33.57128.2-0.28-10.1 3.43 94.32.7274.9-0.71-19.4 5.04 146.24.78138.7-0.26-7.5 5.99 166.47.29202.51.336.1 4.44 157.54.01142.1-0.43-15.4 3.18 83.33.2685.20.081.9 4.25 153.44.49161.90.248.5 6.94 249.16.21223-0.73-26.1 3.29 89.23.0783.4-0.22-5.8 2.64 92.62.9101.60.269 4.05 1093.5595.4-0.5-13.6 3.2 112.33.3115.90.13.6 4.17 106.34.37111.30.25 3.45 119.64.51156.21.0636.6 5.25 152.45.28153.30.030.9 4.44 141.34.54144.70.13.4 2.64 96.42.4489.1-0.2-7.3 4.91 165.65.34180.20.4314.6 3.95 103.53.7297.4-0.23-6.1 3.39 119.62.7998.5-0.6-21.1

PAGE 63

54 Appendix H: Spirometric Measurements Pre FEV1 Pre FEV1 %ile Post FEV1 Po st FEV1 %ileFEV1 Change FEV1 %ile Chg 4.17 1024.26104.30.09 2.3 2.54 88.22.3682-0.18 -6.2 3.53 103.43.48102.2-0.05 -1.2 2.12 74.62.0271.1-0.1 -3.5 3.03 82.83.67100.30.64 17.5 2.64 99.72.95111.20.31 11.5 3.65 73.53.6573.60 0.1 4.42 117.84.2111.9-0.22 -5.9 2.78 98.92.9103.10.12 4.2 4.27 93.14.2893.20.01 0.1 2.89 107.32.5995.9-0.3 -11.4 3.75 81.73.882.70.05 1 2.34 79.92.3379.7-0.01 -0.2 4.42 110.64.37109.3-0.05 -1.3 2.83 91.43.0598.50.22 7.1 2.84 81.22.9885.30.14 4.1 5.41 103.75.41103.60 -0.1 3.67 92.63.6191.2-0.06 -1.4 3.33 115.33.351160.02 0.7 3.87 80.33.8379.5-0.04 -0.8

PAGE 64

55 Appendix I: Respiratory Measurements Distributions Pre FEV1 2 2.5 3 3.5 4 4.5 5 5.5 Quantiles 100.0% maximum 5.4100 99.5% 5.4100 97.5% 5.4100 90.0% 4.4200 75.0% quartile 4.0950 50.0% median 3.4300 25.0% quartile 2.7925 10.0% 2.3600 2.5% 2.1200 0.5% 2.1200 0.0% minimum 2.1200 Moments Mean 3.425 Std Dev 0.8416119 Std Err Mean 0.1881901 upper 95% Mean 3.8188865 lower 95% Mean 3.0311135 N 20

PAGE 65

56 Appendix I: (Continued) Pre FEV1 %ile 70 80 90 100 110 120 Quantiles 100.0% maximum 117.80 99.5% 117.80 97.5% 117.80 90.0% 114.83 75.0% quartile 103.63 50.0% median 92.85 25.0% quartile 81.33 10.0% 75.13 2.5% 73.50 0.5% 73.50 0.0% minimum 73.50 Moments Mean 93.9 Std Dev 13.459843 Std Err Mean 3.0097123 upper 95% Mean 100.1994 lower 95% Mean 87.6006 N 20

PAGE 66

57 Appendix I: (Continued) Post FEV1 2 2.5 3 3.5 4 4.5 5 5.5 Quantiles 100.0% maximum 5.4100 99.5% 5.4100 97.5% 5.4100 90.0% 4.3610 75.0% quartile 4.1075 50.0% median 3.5450 25.0% quartile 2.9125 10.0% 2.3330 2.5% 2.0200 0.5% 2.0200 0.0% minimum 2.0200 Moments Mean 3.4545 Std Dev 0.8318431 Std Err Mean 0.1860058 upper 95% Mean 3.8438145 lower 95% Mean 3.0651855 N 20

PAGE 67

58 Appendix I: (Continued) Post FEV1 %ile 70 80 90 100 110 120 Quantiles 100.0% maximum 116.00 99.5% 116.00 97.5% 116.00 90.0% 111.83 75.0% quartile 104.13 50.0% median 97.20 25.0% quartile 82.17 10.0% 74.19 2.5% 71.10 0.5% 71.10 0.0% minimum 71.10 Moments Mean 94.73 Std Dev 13.468681 Std Err Mean 3.0116886 upper 95% Mean 101.03354 lower 95% Mean 88.426463 N 20

PAGE 68

59 Appendix I: (Continued) Pre R5 2 3 4 5 6 7 Quantiles 100.0% maximum 6.9400 99.5% 6.9400 97.5% 6.9400 90.0% 5.9160 75.0% quartile 4.7925 50.0% median 4.0000 25.0% quartile 3.3150 10.0% 2.6940 2.5% 2.6400 0.5% 2.6400 0.0% minimum 2.6400 Moments Mean 4.125 Std Dev 1.0950775 Std Err Mean 0.2448668 upper 95% Mean 4.637512 lower 95% Mean 3.612488 N 20

PAGE 69

60 Appendix I: (Continued) Pre R5 %ile 100 150 200 250 Quantiles 100.0% maximum 249.10 99.5% 249.10 97.5% 249.10 90.0% 166.32 75.0% quartile 153.15 50.0% median 119.60 25.0% quartile 98.18 10.0% 89.54 2.5% 83.30 0.5% 83.30 0.0% minimum 83.30 Moments Mean 129.815 Std Dev 39.016411 Std Err Mean 8.7243346 upper 95% Mean 148.07524 lower 95% Mean 111.55476 N 20

PAGE 70

61 Appendix I: (Continued) Post R5 2 3 4 5 6 7 8 Quantiles 100.0% maximum 7.2900 99.5% 7.2900 97.5% 7.2900 90.0% 6.1230 75.0% quartile 4.7200 50.0% median 3.8650 25.0% quartile 3.1175 10.0% 2.7270 2.5% 2.4400 0.5% 2.4400 0.0% minimum 2.4400 Moments Mean 4.107 Std Dev 1.2474146 Std Err Mean 0.2789304 upper 95% Mean 4.690808 lower 95% Mean 3.523192 N 20

PAGE 71

62 Appendix I: (Continued) Post R5 %ile 50 100 150 200 Quantiles 100.0% maximum 223.00 99.5% 223.00 97.5% 223.00 90.0% 200.27 75.0% quartile 155.47 50.0% median 122.05 25.0% quartile 95.90 10.0% 83.58 2.5% 74.90 0.5% 74.90 0.0% minimum 74.90 Moments Mean 129.175 Std Dev 41.41872 Std Err Mean 9.2615074 upper 95% Mean 148.55956 lower 95% Mean 109.79044 N 20

PAGE 72

63 Appendix I: (Continued) Pre R20 2.5 3 3.5 4 4.5 5 5.5 Quantiles 100.0% maximum 5.3200 99.5% 5.3200 97.5% 5.3200 90.0% 4.8010 75.0% quartile 3.9500 50.0% median 3.4650 25.0% quartile 3.1825 10.0% 2.6470 2.5% 2.5500 0.5% 2.5500 0.0% minimum 2.5500 Moments Mean 3.595 Std Dev 0.7431901 Std Err Mean 0.1661824 upper 95% Mean 3.9428237 lower 95% Mean 3.2471763 N 20

PAGE 73

64 Appendix I: (Continued) Post R20 2 2.5 3 3.5 4 4.5 5 5.5 6 Quantiles 100.0% maximum 5.9200 99.5% 5.9200 97.5% 5.9200 90.0% 5.1760 75.0% quartile 4.2725 50.0% median 3.2900 25.0% quartile 2.8175 10.0% 2.4950 2.5% 2.3200 0.5% 2.3200 0.0% minimum 2.3200 Moments Mean 3.5795 Std Dev 0.9626579 Std Err Mean 0.2152569 upper 95% Mean 4.0300378 lower 95% Mean 3.1289622 N 20

PAGE 74

65 Appendix I: (Continued) Pre X5 -3.5 -3 -2.5 -2 -1.5 -1 -0.5 Quantiles 100.0% maximum -0.530 99.5% -0.530 97.5% -0.530 90.0% -0.635 75.0% quartile -0.818 50.0% median -1.050 25.0% quartile -1.432 10.0% -2.115 2.5% -3.020 0.5% -3.020 0.0% minimum -3.020 Moments Mean -1.223 Std Dev 0.5911283 Std Err Mean 0.1321803 upper 95% Mean -0.946343 lower 95% Mean -1.499657 N 20

PAGE 75

66 Appendix I: (Continued) Post X5 -3 -2.5 -2 -1.5 -1 -0.5 0 Quantiles 100.0% maximum -0.380 99.5% -0.380 97.5% -0.380 90.0% -0.598 75.0% quartile -0.785 50.0% median -1.010 25.0% quartile -1.408 10.0% -1.594 2.5% -2.580 0.5% -2.580 0.0% minimum -2.580 Moments Mean -1.116 Std Dev 0.4880078 Std Err Mean 0.1091219 upper 95% Mean -0.887605 lower 95% Mean -1.344395 N 20

PAGE 76

67 Appendix I: (Continued) Pre AX 0 5 10 15 20 Quantiles 100.0% maximum 20.040 99.5% 20.040 97.5% 20.040 90.0% 10.975 75.0% quartile 5.977 50.0% median 2.680 25.0% quartile 1.648 10.0% 1.099 2.5% 0.960 0.5% 0.960 0.0% minimum 0.960 Moments Mean 4.578 Std Dev 4.7440984 Std Err Mean 1.0608126 upper 95% Mean 6.7983064 lower 95% Mean 2.3576936 N 20

PAGE 77

68 Appendix I: (Continued) Post AX 0 2.5 5 7.5 10 12.5 15 Quantiles 100.0% maximum 13.260 99.5% 13.260 97.5% 13.260 90.0% 10.840 75.0% quartile 5.918 50.0% median 2.650 25.0% quartile 1.680 10.0% 0.979 2.5% 0.920 0.5% 0.920 0.0% minimum 0.920 Moments Mean 4.1095 Std Dev 3.7563048 Std Err Mean 0.8399353 upper 95% Mean 5.8675048 lower 95% Mean 2.3514952 N 20

PAGE 78

69 Appendix I: (Continued) Pre Fres 7.5 10 12.5 15 17.5 20 22.5 Quantiles 100.0% maximum 21.100 99.5% 21.100 97.5% 21.100 90.0% 20.509 75.0% quartile 14.698 50.0% median 12.555 25.0% quartile 8.777 10.0% 8.383 2.5% 7.980 0.5% 7.980 0.0% minimum 7.980 Moments Mean 12.7465 Std Dev 4.3390616 Std Err Mean 0.9702437 upper 95% Mean 14.777243 lower 95% Mean 10.715757 N 20

PAGE 79

70 Appendix I: (Continued) Post Fres 7.5 10 12.5 15 17.5 20 22.5 Quantiles 100.0% maximum 21.200 99.5% 21.200 97.5% 21.200 90.0% 20.611 75.0% quartile 15.015 50.0% median 11.940 25.0% quartile 8.957 10.0% 8.281 2.5% 7.920 0.5% 7.920 0.0% minimum 7.920 Moments Mean 12.589 Std Dev 4.2574367 Std Err Mean 0.9519918 upper 95% Mean 14.581542 lower 95% Mean 10.596458 N 20

PAGE 80

71 Appendix J: Analysis of Post-test vs Pr e-test Differences in R5, R20 and FEV1 Matched Pairs Difference: Post R5-Pre R5 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5Difference: Post R5-Pre R5 2 3 4 5 6 7 Mean: (Post R5+Pre R5)/2 Post R5 4.107 t-Ratio -0.15236 Pre R5 4.125 DF 19 Mean Difference -0.018 Prob > |t| 0.8805 Std Error 0.11814 Prob > t 0.5597 Upper95% 0.22927 Prob < t 0.4403 Lower95% -0.2653 N 20 Correlation 0.90632 Wilcoxon Sign-Rank Post R5-Pre R5 Test Statistic -18.000 Prob > |z| 0.516 Prob > z 0.742 Prob < z 0.258

PAGE 81

72 Appendix J: (Continued) Matched Pairs Difference: Post R20-Pre R20 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5Difference: Post R20-Pre R20 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 Mean: (Post R20+Pre R20)/2 Post R20 3.5795 t-Ratio -0.13075 Pre R20 3.595 DF 19 Mean Difference -0.0155 Prob > |t| 0.8973 Std Error 0.11855 Prob > t 0.5513 Upper95% 0.23262 Prob < t 0.4487 Lower95% -0.2636 N 20 Correlation 0.83723 Wilcoxon Sign-Rank Post R20-Pre R20 Test Statistic -27.000 Prob > |z| 0.330 Prob > z 0.835 Prob < z 0.165

PAGE 82

73 Appendix J: (Continued) Matched Pairs Difference: Post FEV1-Pre FEV1 -1.0 -0.5 0.0 0.5 1.0Difference: Post FEV1-Pre FEV1 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 Mean: (Post FEV1+Pre FEV1)/2 Post FEV1 3.4545 t-Ratio 0.654114 Pre FEV1 3.425 DF 19 Mean Difference 0.0295 Prob > |t| 0.5209 Std Error 0.0451 Prob > t 0.2604 Upper95% 0.12389 Prob < t 0.7396 Lower95% -0.0649 N 20 Correlation 0.97102 Wilcoxon Sign-Rank Post FEV1-Pre FEV1 Test Statistic 7.000 Prob > |z| 0.775 Prob > z 0.387 Prob < z 0.613


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Caffeine and airway resistance
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[Tampa, Fla.] :
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ABSTRACT: This study investigated the effect of caffeine on airway resistance. The subjects were drawn from volunteers (18-90 years old) in good health, with no major cardiopulmonary conditions. We found no association between the consumption of a single cup of the caffeinated beverage coffee and a decrease in airway resistance within one hour in a normal sample of subjects as measured by impulse oscillometry nor with conventional spirometry It appears that any possible bronchodilatory effect of the caffeine from a single cup of coffee in a normal population is below the limit of detection of spirometry and impulse oscillometry or is not sufficiently expressed in the one hour time frame of the study. The study did validate currently accepted methods of using the Jaeger impulse oscillometry (IOS) measurement for use at the University of South Florida (USF). The impulse oscillometry technique was found to be a useful adjunct to conventional pulmonary function testing.Conventional pulmonary function testing provides a useful measure of a person's ability to breathe yet is difficult to perform and only indirectly guides the physician to the diagnosis of the pathology behind the person's breathing difficulties. The impulse oscillometry technique may help the physician to noninvasively determine the location of a pulmonary obstruction by measurement of the dynamics of sound wave travel through the airways of the lungs.
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