- Email: [email protected]
Prevalence of Cocaine Use and Its Impact on Asthma Exacerbation in an Urban Population
Prevalence of Cocaine Use and Its Impact on Asthma Exacerbation in an Urban Population* Lauren A. Rome, MD; Michael L. Lippmann, MD, FCCP; William C. Dalsey, MD; Pamela Taggart, PhD; and Sherry Pomerantz, PhD
Objectives: To assess the prevalence of cocaine use, and its impact on severity of presentation, among adults presenting to the emergency department (ED) with asthma. A secondary aim was to assess the use of various asthma treatment modalities, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines. Methods: All adults aged 18 to 55 years who presented to the ED of this institution with an asthma attack, were approached about participating in the study, which required giving informed consent, answering a facilitated questionnaire, and giving a urine sample for drug screening. Results: Patients were enrolled during a 7-month period. A total of 163 patients were approached to enter the study; 116 patients consented to participate in the study, with 103 submitting complete urine samples. Thirty-seven patients refused to participate, and 10 were excluded. Sixty-eight percent of the patients were women, with a mean age of 33 years. African-Americans made up 89% of the total group. Thirty-five percent were cigarette smokers. Urine cocaine tests were positive in 13 of 103 (13%); 6 of 103 (5.8%) were positive for opiates. In the cocaine-positive group, 5 of 13 patients (38%) were admitted to the hospital, including two patients requiring intubation and mechanical ventilation. Of the total group, 23 of 103 patients (22%) were admitted, and 5 of those 23 admitted patients (22%) were cocaine-positive. Length of stay was significantly longer (5 vs 2.5 days, p < 0.05) in the cocaine-positive admitted patients. Forty-six percent of all patients reported using inhaled corticosteroids (ICS), with 39% of admitted patients using them. Thirty-two percent of all patients had obtained three or more refills of their 2-agonist inhaler in the previous month. Conclusions: The prevalence of cocaine use may be much higher than the 13% shown in this study, because of patients’ refusal to participate in the study. Second, the severity of exacerbation appears to be worse in the cocaine-positive group. Finally, the majority of patients presenting did not use ICS in accordance with the NAEPP guidelines. (CHEST 2000; 117:1324 –1329) Key words: asthma; cocaine; substance abuse Abbreviations: ED ⫽ emergency department; ICS ⫽ inhaled corticosteroids; NAEPP ⫽ National Asthma Education and Prevention Program
from asthma has been increasing, raisM ortality ing questions about the increasing prevalence and severity of asthma, as well as about the potential effects of changes in the medical management of asthma. Leikauf et al1 attribute the increasing prevalence and mortality to be more likely related to *From the Division of Pulmonary Medicine, Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA. Supported by the Division of Pulmonary Medicine, Albert Einstein Medical Center. Manuscript received June 22, 1999; revision accepted January 11, 2000. Correspondence to: Michael Lippmann, MD, FCCP, Albert Einstein Medical Center, Department of Medicine, Pulmonary Division, 5401 Old York Rd., Suite 363, Philadelphia, PA 19141; e-mail: [email protected] 1324
environmental than genetic factors. Asthma deaths are particularly high in lower socioeconomic groups, which may be accounted for by several factors, including crowded living conditions, poor access to health care, and lack of patient education about asthma.2 Another important consideration is that of illicit drug use, particularly crack cocaine use, which is a major social problem in the United States, particularly in large urban populations. A number of cases illustrating a temporal association between heavy crack use and severe acute exacerbation of asthma, including fatal asthma, have been reported.3– 6 The increase in cocaine use seems to parallel the increase in asthma morbidity and mortality, suggesting there may be an association between the two. Levenson et Clinical Investigations
al7 reviewed cases of asthma deaths in the Chicago area. Their findings were that 29 of 92 cases (31.5%) were confounded by substance abuse (including cocaine) or alcohol use. Thus far, the prevalence of cocaine use among patients presenting with acute asthma is unknown, and crack cocaine may be unrecognized as a precipitant for asthma exacerbations. This study addresses the prevalence of illicit drug use—particularly cocaine—among adults presenting to an inner-city emergency department (ED), and the relationship of cocaine use and severity of asthma exacerbation. A secondary aim was to assess the frequency of use of various treatment modalities for asthma, particularly inhaled corticosteroids (ICS) and 2-agonists, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines.8
Materials and Methods We conducted a prospective study to determine the prevalence of cocaine use and its impact on severity in adult patients presenting to an inner-city ED with acute asthma exacerbation. Patients between the ages of 18 and 55 years, who presented to the ED between 8:00 am and midnight 7 days a week and who were assessed to be having an acute asthma exacerbation, were eligible to be included in the study. Patients with other diagnoses such as COPD and congestive heart failure were excluded. This was a prospective study during which patients were interviewed to determine the extent of cocaine and opiate use as well as treatment modalities being administered. Approval from the hospital’s institutional review board was obtained. Informed consent was obtained from patients entering the study, which involved completing a facilitated questionnaire and providing a urine sample for drug screening (cocaine and opiates). One hundred sixteen patients were interviewed. Complete data, including urine screens, were available for 103 subjects. A research facilitator conducted the interview (Fig 1). Questions assessed prior asthma severity and management (including use of ICS and 2-agonists), as well as history of tobacco, alcohol, and illicit drug use. Information regarding the patient’s current presentation, ED treatment, and disposition were documented on a data collection form by the facilitator. Patients who were too ill on initial presentation to consent to the study were approached later once their condition stabilized. Urine samples were analyzed for the presence of the cocaine metabolite benzoylecgonine, as well as for opiates, using the Axsym system (Abbott Laboratories; Abbott Park, IL). (A cutoff value of ⬎ 300 ng/mL is considered to be a positive result for a cocaine metabolite assay by our hospital laboratory, as recommended by the National Institute on Drug Abuse.) The prevalence of positive cocaine screens was assessed; all clinical data were entered into a database and were analyzed using computer software (SPSS for Windows, version 7.5; SPSS; Chicago, IL).
Results Patients were enrolled during a 7-month period (January 14, 1998, through August 25, 1998). One
hundred sixty-three patients were approached to enter the study: of these, 116 patients consented to the study, completing the questionnaire and giving urine samples. There were 103 complete urine samples and 13 missing urine test results. Thirty-seven patients (ie, 29% of the total group) refused to participate; in addition, 10 patients were excluded because of language barriers, psychiatric problem, not having an interviewer present, or inability to consent owing to severity of illness. The patients were mostly women (68%), with a mean (⫾ SD) age of 33 ⫾ 9.9 years. African-Americans made up 89%, with the remainder being white (5%), Hispanic (3%), and Asian (2%). Forty-nine percent of the total group were current tobacco smokers (Table 1). Patients who tested positive for cocaine were more likely to be tobacco smokers than those who tested negative (p ⬍ 0.05). The results of cocaine tests were positive in 13 of 103 patients (13%); only 3 of these patients admitted to cocaine use (all in the form of crack) on questioning. Opiates were positive in 6 of 103 patients (5.8%); 3 of these patients tested positive for cocaine as well. Hospital admission was required for 23 of 103 patients (22%) of the whole patient group. Mean peak expiratory flow rates were 163 L/min for the cocaine-positive patients and 192 L/min for the cocaine-negative patients. Fifty-six percent of all patients had visited an ED three times in the preceding year, with a mean of 3.8 visits. There was no significant difference between the cocaine-positive and cocaine-negative groups in this regard. There appeared to be an increased rate of hospital admissions among the cocaine-positive group (38%) compared with the cocaine-negative group (20%), although this difference did not reach statistical significance (p ⫽ 0.138). Of the admitted patients, 5 of 23 (22%) had positive results of cocaine tests, with 2 of 3 intubated patients being cocaine-positive. Length of hospital stay was found to be significantly longer in the cocaine-positive admitted patients, with a mean of 5 days, compared with the cocainenegative admitted patients, whose average length of stay was 2.5 days (p ⫽ 0.03; Table 2). Only 45% of all patients were using ICS, even though virtually all of these patients were classified as being at least in the mild persistent category of severity, thus warranting the use of ICS as per the NAEPP guidelines. In the admitted group, 9 of 23 patients (39%) were using ICS, compared with 37 of 76 (49%) of those discharged. No patients had a recollection of the use of nonsteroidal inhaled anti-inflammatory agents or leukotriene antagonists. Thirty-two percent of all patients had obtained three or more refills of their 2-agonist inhaler in the previous month. CHEST / 117 / 5 / MAY, 2000
1325
Figure 1. Study questionnaire.
Discussion Our results found a prevalence of 13% positive results of cocaine tests in our adult asthmatic population. The actual prevalence may be much higher, partly because of a high rate of refusal (29%) to participate in this study. Unfortunately, only a small proportion of cocaine-positive patients actually admitted to its use, underscoring the lack of reliability of self-reporting of drug abuse. Furthermore, we were unable to ascertain the route, acuity, and intensity of cocaine use in the majority of cases. The 1326
relatively high percentage of positive cocaine screens in the admitted patient group, particularly in the intubated patients, may suggest that cocaine use is associated with a more severe asthma exacerbation, although the number of patients was small. In addition, the cocaine-positive patients had a significantly longer length of hospital stay, which leads to increased costs of care. Unfortunately, we were unable to control for many potentially confounding factors, such as access to health care, appropriate use of medications, tobacco smoking, or effects of other Clinical Investigations
Table 1—Comparison of Cocaine-Positive and Cocaine-Negative Patients* Variable Age, yr (SD) Sex Male Female Race African-American White Hispanic Asian Smoking tobacco ICS use 2-agonist refills in prior month, No. (SD) ED visits in prior year, No. (SD) PEF–initial, L/min (SD) Admitted Intubated
Total Group (n ⫽ 103)
Cocaine-Positive (n ⫽ 13)
Cocaine-Negative (n ⫽ 90)
p Value†
33 (9.9)
34 (9.9)
33.6 (9.6)
NS
33 (32%) 70 (68%)
7 6
26 6
NS NS
92 6 3 2 36/73 (49%) 46/99 (46%) 1.23 (1.4) 3.8 (4.7) 190 (7) 23/103 (22%) 3
13
79 6 3 2 27/62 (36%) 41/86 (48%) 1.3 (1.5) 3.6 (4.5) 192 (78) 18/90 (20%) 1/3
0.02 NS NS NS NS 0.138 NS
9/12 (75%) 5/13 (38%) 0.8 (0.9) 4.9 (5.9) 162.5 (56) 5/13 (38%) 2/3
* PEF ⫽ peak expiratory flow rate; NS ⫽ not significant. †Difference between cocaine-positive group and cocaine-negative group.
drugs and environmental factors. To better elucidate the relevance of recent cocaine use to acute asthma, it would have been helpful to obtain urine drug screens on nonasthmatic control subjects. We were hampered in this regard by the requirement to obtain informed consent. Another finding was that the majority of patients seeking treatment at this ED do not use ICS in accordance with the 1997 NAEPP guidelines.8 In the last century, cocaine was used as an ingredient in tonics used for curing asthma.9 That cocaine may precipitate asthma was first recognized in 1932 in a young girl treated with nasal cocaine for anesthesia.3 Cases of cocaine-precipitated bronchospasm, in-
cluding severe or life-threatening exacerbations of bronchospasm, have been described in the literature.4 – 6 These effects are more commonly seen in cocaine use in the form of freebasing or crack. Crack cocaine results in quicker absorption and euphoria than nasal insufflation or snorting and avoids the use of needles required for the IV route, which also provides instantaneous euphoria. Free-base is a cocaine alkaloid that melts at 98°C, vaporizes at higher temperatures, and is heat-stable, thus allowing the drug to be smoked.6,10 Free-base is usually prepared by mixing cocaine hydrochloride and baking soda, which is then boiled in water and cooled. The precipitate is either filtered or extracted by adding a solvent such as ether or alcohol. The cocaine remains
Table 2—Hospitalized Asthma Patients: Comparing Cocaine-Positive and Cocaine-Negative Patients* Variable Age, yr (SD) Sex Male Female Race African-American White Smoking tobacco ICS use 2-agonist refills in prior month, No. (SD) ED visits in 1 yr, No. (SD) PEF–initial, L/min† Length of stay, d
Hospitalized Patients (n ⫽ 23)
Cocaine-Positive (n ⫽ 5)
Cocaine-Negative (n ⫽ 18)
39 (8.7)
42 (7.7)
38 (9)
11 12
3 2
8 10
22 1 8/23 (35%) 9/23 (39%) 1.7 (1.6) 5 (1.7) 146 3
5
17 1 6/18 (33%) 5/18 (28%) 1.7 (1.8) 4.7 (5.4) 145 2.5
2/5 (40%) 4/5 (80%) 1.75 (0.96) 6.3 (9.9) 140 5‡
*See Table 1 footnote for abbreviations. †Of 15 hospitalized patients whose initial PEF was measured, 1 tested positive for cocaine and 14 tested negative for cocaine. ‡p ⫽ 0.03 by Mann-Whitney U test. CHEST / 117 / 5 / MAY, 2000
1327
dissolved in the solvent, which can be evaporated, leaving the relatively pure base as a residue. The simpler crack method allows the alkaloidal cocaine to precipitate without a solvent extraction method. Cocaine may then be smoked using various methods, such as a glass or regular pipe, or by mixing cocaine with tobacco or marijuana in cigarette form.10 This method of use is most irritating to the bronchial epithelium; bronchospasm may be a result of inflammation of the respiratory epithelium by either cocaine or adulterants. In a study comparing the acute effects of inhaled vs IV cocaine on airway dynamics,11 it was demonstrated that smoked cocaine base caused bronchoconstriction, whereas a similar intoxicating dose of IV cocaine did not. The most likely mechanism is because of a topical irritant effect of the cocaine or the contaminants with which it is mixed. IgE-mediated sensitivity to cocaine may also be a factor in some cases.6 Asthmatic patients who smoke cocaine may be at high risk for developing severe exacerbations of their asthma, depending on the degree of airways hyperresponsiveness, the dose of inhaled cocaine, and the nature of the contaminants inhaled during crack smoking.11 The reported prevalence of cocaine use varies significantly because of selection and reporting biases. In the 1980s, Drug Abuse Warning Network data reflected an increase to 5.7 million regular cocaine users in the country by the end of the decade.12 Data from the 1997 National Household Survey on Drug Abuse estimates 1.5 million Americans aged ⱖ 12 years are regular cocaine users.13 However, the Office of National Drug Control Policy estimates the number of chronic cocaine users to be 3.6 million. About 40% of cocaine users use cocaine in the form of crack (National Household Survey on Drug Abuse data). It is the leading cause of illicit drug-related visits to EDs in the United States.14,15 In a prospective study by McNagny et al,14 the prevalence of cocaine use in young men presenting to an inner-city walk-in clinic was determined to be 39% by urine testing; 72% of those testing positive denied illicit drug use in the prior 3 days. In our study, only 3 of the 13 patients who tested positive for cocaine actually admitted to its use. In the study by McNagny et al,14 consent was not obtained for drug screening. The results of the aforementioned study emphasize the magnitude of the cocaine epidemic and indicate the unreliability of self-reporting of illicit drug use. In another study, ED patients with new-onset bronchospasm were tested for cocaine metabolites, with 21 of 59 having positive results (36%).16 This was compared with a control group of randomly selected, age- and sex-matched individuals without a history of respiratory disease, in which 15% tested positive for cocaine. This finding signifies an 1328
association between cocaine use and new-onset bronchospasm or recrudescence of asthma. In a similar study by Gaeta and Hammock,17 44% of asthmatics admitted to or tested positive for illicit drugs, compared with 20% of control patients. These studies were prospective in design. It is important to recognize that in these studies, in contrast with ours, written consent was not a requirement to perform urine drug screening. This was an important factor inasmuch as a significant number of patients declined to participate in our study. In addition to causing asthma exacerbations, crack cocaine use has a number of other pulmonary complications associated with its use: acute respiratory symptoms, thermal airway injury, deterioration in lung function, pneumothorax and pneumomediastinum, bronchiolitis obliterans with organizing pneumonia, pulmonary hemorrhage, noncardiogenic pulmonary edema, pulmonary infiltrates with eosinophilia, and pulmonary vascular disease.10,18 –22 Inhalation of freebase cocaine has been shown to be associated with interstitial lung disease, with a reduction in diffusing capacity in some studies.20 The increase in prevalence of cocaine use in the United States may be an important factor responsible for increasing asthma severity and mortality, despite major advances in treatment modalities. Our study and others16,17 point to a relatively high prevalence of cocaine use among patients with asthma exacerbation, possibly contributing to the increase in asthma morbidity. An important implication of our study is to emphasize the importance for physicians to be alert to the possibility of crack cocaine as a precipitating factor for acute asthma. Improved access to health care and patient education, in addition to physician awareness of and adherence to NAEPP guidelines in treating asthma, are important factors in improving outcomes in asthma in this population. References 1 Leikauf GD, Kline S, Albert RE, et al. Evaluation of a possible association of urban air toxics and asthma. Environ Health Perspect 1995; 103:253–271 2 Lang DM, Polansky M. Patterns of asthma mortality in Philadelphia from 1969 to 1991. N Engl J Med 1994; 331:1542–1546 3 Waldbott GC. Asthma due to a local anesthetic. JAMA 1932; 99:1942 4 Rubin RB, Neugarten J. Cocaine-associated asthma. Am J Med 1990; 88:428 – 439 5 Rao AN, Polos PG, Walther FA. Crack abuse and asthma: a fatal combination. N Y State J Med 1990; 90:511–512 6 Rebuhn J. Association of asthma and freebase smoking. Ann Allergy 1988; 60:339 –342 7 Levenson T, Greenberger PA, Donoghue R, et al. Asthma deaths confounded by substance abuse. Chest 1996; 110:604 – 610 8 National Asthma Education Program. Expert panel report 2: Clinical Investigations
9 10 11 12
13 14
guidelines for the diagnosis and management of asthma. Bethesda, MD: US Dept of Health and Human Services, National Heart, Lung, and Blood Institute; 1997. NIH publication 97– 4051 Cohen SG. Asthma among the famous: Nathan Tucker (1838 –1920), American physician. Allergy Asthma Proc 1997; 18:252–255 Haim DY, Lippmann ML, Goldberg SK, et al. The pulmonary complications of crack cocaine. Chest 1995; 107:233–240 Tashkin DP, Kleerup EC, Koyal SN, et al. Acute effects of inhaled and IV cocaine on airway dynamics. Chest 1996; 110:904 –910 Drug Abuse Warning Network. Semiannual Report: trend data through January-July 1988. Rockville, MD: US Dept of Health and Human Services, National Institute of Drug Abuse; 1989. DHHS publication ADM89 –1607 National Institute on Drug Abuse. Research report series: cocaine abuse and addiction 1999. Bethesda, MD: National Institutes of Health, 1999; NIH publication No. 99-4342 McNagny SE, Parker RM. High prevalence of recent cocaine use and the unreliability of patient self-report in an inner-city walk-in clinic. JAMA 1992; 267:1106 –1108
15 Rich JA, Singer DE. Cocaine-related symptoms in patients presenting to an urban emergency department. Ann Emerg Med 1991; 20:616 – 621 16 Osborn HM, Tang M, Bradley K, et al. New-onset bronchospasm or recrudescence of asthma associated with cocaine abuse. Acad Emerg Med 1997; 4:689 – 692 17 Gaeta TJ, Hammock R. Association between substance abuse and acute exacerbation of bronchial asthma [letter]. Acad Emerg Med 1996; 3:1170 –1172 18 Tashkin DP, Khalsa M, Gorelick D, et al. Pulmonary status of habitual cocaine smokers. Am Rev Respir Dis 1992; 145:92–100 19 Kissner DG, Lawrence WD, Selis JE, et al. Crack lung: pulmonary disease caused by cocaine abuse. Am Rev Respir Dis 1987; 136:1250 –1252 20 Albertson TE, Walby WF, Derlet RW. Stimulant-induced pulmonary toxicity. Chest 1995; 108:1140 –1149 21 Klinger JR, Bensadoun E, Corrao W. Pulmonary complications from alveolar accumulation of carbonaceous material in a cocaine smoker. Chest 1992; 101:1171–1173 22 Itkonen J, Schnoll S, Glassroth J. Pulmonary dysfunction in “freebase” cocaine users. Arch Intern Med 1984; 144:2195– 2197
CHEST / 117 / 5 / MAY, 2000
1329
Objectives: To assess the prevalence of cocaine use, and its impact on severity of presentation, among adults presenting to the emergency department (ED) with asthma. A secondary aim was to assess the use of various asthma treatment modalities, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines. Methods: All adults aged 18 to 55 years who presented to the ED of this institution with an asthma attack, were approached about participating in the study, which required giving informed consent, answering a facilitated questionnaire, and giving a urine sample for drug screening. Results: Patients were enrolled during a 7-month period. A total of 163 patients were approached to enter the study; 116 patients consented to participate in the study, with 103 submitting complete urine samples. Thirty-seven patients refused to participate, and 10 were excluded. Sixty-eight percent of the patients were women, with a mean age of 33 years. African-Americans made up 89% of the total group. Thirty-five percent were cigarette smokers. Urine cocaine tests were positive in 13 of 103 (13%); 6 of 103 (5.8%) were positive for opiates. In the cocaine-positive group, 5 of 13 patients (38%) were admitted to the hospital, including two patients requiring intubation and mechanical ventilation. Of the total group, 23 of 103 patients (22%) were admitted, and 5 of those 23 admitted patients (22%) were cocaine-positive. Length of stay was significantly longer (5 vs 2.5 days, p < 0.05) in the cocaine-positive admitted patients. Forty-six percent of all patients reported using inhaled corticosteroids (ICS), with 39% of admitted patients using them. Thirty-two percent of all patients had obtained three or more refills of their 2-agonist inhaler in the previous month. Conclusions: The prevalence of cocaine use may be much higher than the 13% shown in this study, because of patients’ refusal to participate in the study. Second, the severity of exacerbation appears to be worse in the cocaine-positive group. Finally, the majority of patients presenting did not use ICS in accordance with the NAEPP guidelines. (CHEST 2000; 117:1324 –1329) Key words: asthma; cocaine; substance abuse Abbreviations: ED ⫽ emergency department; ICS ⫽ inhaled corticosteroids; NAEPP ⫽ National Asthma Education and Prevention Program
from asthma has been increasing, raisM ortality ing questions about the increasing prevalence and severity of asthma, as well as about the potential effects of changes in the medical management of asthma. Leikauf et al1 attribute the increasing prevalence and mortality to be more likely related to *From the Division of Pulmonary Medicine, Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA. Supported by the Division of Pulmonary Medicine, Albert Einstein Medical Center. Manuscript received June 22, 1999; revision accepted January 11, 2000. Correspondence to: Michael Lippmann, MD, FCCP, Albert Einstein Medical Center, Department of Medicine, Pulmonary Division, 5401 Old York Rd., Suite 363, Philadelphia, PA 19141; e-mail: [email protected] 1324
environmental than genetic factors. Asthma deaths are particularly high in lower socioeconomic groups, which may be accounted for by several factors, including crowded living conditions, poor access to health care, and lack of patient education about asthma.2 Another important consideration is that of illicit drug use, particularly crack cocaine use, which is a major social problem in the United States, particularly in large urban populations. A number of cases illustrating a temporal association between heavy crack use and severe acute exacerbation of asthma, including fatal asthma, have been reported.3– 6 The increase in cocaine use seems to parallel the increase in asthma morbidity and mortality, suggesting there may be an association between the two. Levenson et Clinical Investigations
al7 reviewed cases of asthma deaths in the Chicago area. Their findings were that 29 of 92 cases (31.5%) were confounded by substance abuse (including cocaine) or alcohol use. Thus far, the prevalence of cocaine use among patients presenting with acute asthma is unknown, and crack cocaine may be unrecognized as a precipitant for asthma exacerbations. This study addresses the prevalence of illicit drug use—particularly cocaine—among adults presenting to an inner-city emergency department (ED), and the relationship of cocaine use and severity of asthma exacerbation. A secondary aim was to assess the frequency of use of various treatment modalities for asthma, particularly inhaled corticosteroids (ICS) and 2-agonists, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines.8
Materials and Methods We conducted a prospective study to determine the prevalence of cocaine use and its impact on severity in adult patients presenting to an inner-city ED with acute asthma exacerbation. Patients between the ages of 18 and 55 years, who presented to the ED between 8:00 am and midnight 7 days a week and who were assessed to be having an acute asthma exacerbation, were eligible to be included in the study. Patients with other diagnoses such as COPD and congestive heart failure were excluded. This was a prospective study during which patients were interviewed to determine the extent of cocaine and opiate use as well as treatment modalities being administered. Approval from the hospital’s institutional review board was obtained. Informed consent was obtained from patients entering the study, which involved completing a facilitated questionnaire and providing a urine sample for drug screening (cocaine and opiates). One hundred sixteen patients were interviewed. Complete data, including urine screens, were available for 103 subjects. A research facilitator conducted the interview (Fig 1). Questions assessed prior asthma severity and management (including use of ICS and 2-agonists), as well as history of tobacco, alcohol, and illicit drug use. Information regarding the patient’s current presentation, ED treatment, and disposition were documented on a data collection form by the facilitator. Patients who were too ill on initial presentation to consent to the study were approached later once their condition stabilized. Urine samples were analyzed for the presence of the cocaine metabolite benzoylecgonine, as well as for opiates, using the Axsym system (Abbott Laboratories; Abbott Park, IL). (A cutoff value of ⬎ 300 ng/mL is considered to be a positive result for a cocaine metabolite assay by our hospital laboratory, as recommended by the National Institute on Drug Abuse.) The prevalence of positive cocaine screens was assessed; all clinical data were entered into a database and were analyzed using computer software (SPSS for Windows, version 7.5; SPSS; Chicago, IL).
Results Patients were enrolled during a 7-month period (January 14, 1998, through August 25, 1998). One
hundred sixty-three patients were approached to enter the study: of these, 116 patients consented to the study, completing the questionnaire and giving urine samples. There were 103 complete urine samples and 13 missing urine test results. Thirty-seven patients (ie, 29% of the total group) refused to participate; in addition, 10 patients were excluded because of language barriers, psychiatric problem, not having an interviewer present, or inability to consent owing to severity of illness. The patients were mostly women (68%), with a mean (⫾ SD) age of 33 ⫾ 9.9 years. African-Americans made up 89%, with the remainder being white (5%), Hispanic (3%), and Asian (2%). Forty-nine percent of the total group were current tobacco smokers (Table 1). Patients who tested positive for cocaine were more likely to be tobacco smokers than those who tested negative (p ⬍ 0.05). The results of cocaine tests were positive in 13 of 103 patients (13%); only 3 of these patients admitted to cocaine use (all in the form of crack) on questioning. Opiates were positive in 6 of 103 patients (5.8%); 3 of these patients tested positive for cocaine as well. Hospital admission was required for 23 of 103 patients (22%) of the whole patient group. Mean peak expiratory flow rates were 163 L/min for the cocaine-positive patients and 192 L/min for the cocaine-negative patients. Fifty-six percent of all patients had visited an ED three times in the preceding year, with a mean of 3.8 visits. There was no significant difference between the cocaine-positive and cocaine-negative groups in this regard. There appeared to be an increased rate of hospital admissions among the cocaine-positive group (38%) compared with the cocaine-negative group (20%), although this difference did not reach statistical significance (p ⫽ 0.138). Of the admitted patients, 5 of 23 (22%) had positive results of cocaine tests, with 2 of 3 intubated patients being cocaine-positive. Length of hospital stay was found to be significantly longer in the cocaine-positive admitted patients, with a mean of 5 days, compared with the cocainenegative admitted patients, whose average length of stay was 2.5 days (p ⫽ 0.03; Table 2). Only 45% of all patients were using ICS, even though virtually all of these patients were classified as being at least in the mild persistent category of severity, thus warranting the use of ICS as per the NAEPP guidelines. In the admitted group, 9 of 23 patients (39%) were using ICS, compared with 37 of 76 (49%) of those discharged. No patients had a recollection of the use of nonsteroidal inhaled anti-inflammatory agents or leukotriene antagonists. Thirty-two percent of all patients had obtained three or more refills of their 2-agonist inhaler in the previous month. CHEST / 117 / 5 / MAY, 2000
1325
Figure 1. Study questionnaire.
Discussion Our results found a prevalence of 13% positive results of cocaine tests in our adult asthmatic population. The actual prevalence may be much higher, partly because of a high rate of refusal (29%) to participate in this study. Unfortunately, only a small proportion of cocaine-positive patients actually admitted to its use, underscoring the lack of reliability of self-reporting of drug abuse. Furthermore, we were unable to ascertain the route, acuity, and intensity of cocaine use in the majority of cases. The 1326
relatively high percentage of positive cocaine screens in the admitted patient group, particularly in the intubated patients, may suggest that cocaine use is associated with a more severe asthma exacerbation, although the number of patients was small. In addition, the cocaine-positive patients had a significantly longer length of hospital stay, which leads to increased costs of care. Unfortunately, we were unable to control for many potentially confounding factors, such as access to health care, appropriate use of medications, tobacco smoking, or effects of other Clinical Investigations
Table 1—Comparison of Cocaine-Positive and Cocaine-Negative Patients* Variable Age, yr (SD) Sex Male Female Race African-American White Hispanic Asian Smoking tobacco ICS use 2-agonist refills in prior month, No. (SD) ED visits in prior year, No. (SD) PEF–initial, L/min (SD) Admitted Intubated
Total Group (n ⫽ 103)
Cocaine-Positive (n ⫽ 13)
Cocaine-Negative (n ⫽ 90)
p Value†
33 (9.9)
34 (9.9)
33.6 (9.6)
NS
33 (32%) 70 (68%)
7 6
26 6
NS NS
92 6 3 2 36/73 (49%) 46/99 (46%) 1.23 (1.4) 3.8 (4.7) 190 (7) 23/103 (22%) 3
13
79 6 3 2 27/62 (36%) 41/86 (48%) 1.3 (1.5) 3.6 (4.5) 192 (78) 18/90 (20%) 1/3
0.02 NS NS NS NS 0.138 NS
9/12 (75%) 5/13 (38%) 0.8 (0.9) 4.9 (5.9) 162.5 (56) 5/13 (38%) 2/3
* PEF ⫽ peak expiratory flow rate; NS ⫽ not significant. †Difference between cocaine-positive group and cocaine-negative group.
drugs and environmental factors. To better elucidate the relevance of recent cocaine use to acute asthma, it would have been helpful to obtain urine drug screens on nonasthmatic control subjects. We were hampered in this regard by the requirement to obtain informed consent. Another finding was that the majority of patients seeking treatment at this ED do not use ICS in accordance with the 1997 NAEPP guidelines.8 In the last century, cocaine was used as an ingredient in tonics used for curing asthma.9 That cocaine may precipitate asthma was first recognized in 1932 in a young girl treated with nasal cocaine for anesthesia.3 Cases of cocaine-precipitated bronchospasm, in-
cluding severe or life-threatening exacerbations of bronchospasm, have been described in the literature.4 – 6 These effects are more commonly seen in cocaine use in the form of freebasing or crack. Crack cocaine results in quicker absorption and euphoria than nasal insufflation or snorting and avoids the use of needles required for the IV route, which also provides instantaneous euphoria. Free-base is a cocaine alkaloid that melts at 98°C, vaporizes at higher temperatures, and is heat-stable, thus allowing the drug to be smoked.6,10 Free-base is usually prepared by mixing cocaine hydrochloride and baking soda, which is then boiled in water and cooled. The precipitate is either filtered or extracted by adding a solvent such as ether or alcohol. The cocaine remains
Table 2—Hospitalized Asthma Patients: Comparing Cocaine-Positive and Cocaine-Negative Patients* Variable Age, yr (SD) Sex Male Female Race African-American White Smoking tobacco ICS use 2-agonist refills in prior month, No. (SD) ED visits in 1 yr, No. (SD) PEF–initial, L/min† Length of stay, d
Hospitalized Patients (n ⫽ 23)
Cocaine-Positive (n ⫽ 5)
Cocaine-Negative (n ⫽ 18)
39 (8.7)
42 (7.7)
38 (9)
11 12
3 2
8 10
22 1 8/23 (35%) 9/23 (39%) 1.7 (1.6) 5 (1.7) 146 3
5
17 1 6/18 (33%) 5/18 (28%) 1.7 (1.8) 4.7 (5.4) 145 2.5
2/5 (40%) 4/5 (80%) 1.75 (0.96) 6.3 (9.9) 140 5‡
*See Table 1 footnote for abbreviations. †Of 15 hospitalized patients whose initial PEF was measured, 1 tested positive for cocaine and 14 tested negative for cocaine. ‡p ⫽ 0.03 by Mann-Whitney U test. CHEST / 117 / 5 / MAY, 2000
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dissolved in the solvent, which can be evaporated, leaving the relatively pure base as a residue. The simpler crack method allows the alkaloidal cocaine to precipitate without a solvent extraction method. Cocaine may then be smoked using various methods, such as a glass or regular pipe, or by mixing cocaine with tobacco or marijuana in cigarette form.10 This method of use is most irritating to the bronchial epithelium; bronchospasm may be a result of inflammation of the respiratory epithelium by either cocaine or adulterants. In a study comparing the acute effects of inhaled vs IV cocaine on airway dynamics,11 it was demonstrated that smoked cocaine base caused bronchoconstriction, whereas a similar intoxicating dose of IV cocaine did not. The most likely mechanism is because of a topical irritant effect of the cocaine or the contaminants with which it is mixed. IgE-mediated sensitivity to cocaine may also be a factor in some cases.6 Asthmatic patients who smoke cocaine may be at high risk for developing severe exacerbations of their asthma, depending on the degree of airways hyperresponsiveness, the dose of inhaled cocaine, and the nature of the contaminants inhaled during crack smoking.11 The reported prevalence of cocaine use varies significantly because of selection and reporting biases. In the 1980s, Drug Abuse Warning Network data reflected an increase to 5.7 million regular cocaine users in the country by the end of the decade.12 Data from the 1997 National Household Survey on Drug Abuse estimates 1.5 million Americans aged ⱖ 12 years are regular cocaine users.13 However, the Office of National Drug Control Policy estimates the number of chronic cocaine users to be 3.6 million. About 40% of cocaine users use cocaine in the form of crack (National Household Survey on Drug Abuse data). It is the leading cause of illicit drug-related visits to EDs in the United States.14,15 In a prospective study by McNagny et al,14 the prevalence of cocaine use in young men presenting to an inner-city walk-in clinic was determined to be 39% by urine testing; 72% of those testing positive denied illicit drug use in the prior 3 days. In our study, only 3 of the 13 patients who tested positive for cocaine actually admitted to its use. In the study by McNagny et al,14 consent was not obtained for drug screening. The results of the aforementioned study emphasize the magnitude of the cocaine epidemic and indicate the unreliability of self-reporting of illicit drug use. In another study, ED patients with new-onset bronchospasm were tested for cocaine metabolites, with 21 of 59 having positive results (36%).16 This was compared with a control group of randomly selected, age- and sex-matched individuals without a history of respiratory disease, in which 15% tested positive for cocaine. This finding signifies an 1328
association between cocaine use and new-onset bronchospasm or recrudescence of asthma. In a similar study by Gaeta and Hammock,17 44% of asthmatics admitted to or tested positive for illicit drugs, compared with 20% of control patients. These studies were prospective in design. It is important to recognize that in these studies, in contrast with ours, written consent was not a requirement to perform urine drug screening. This was an important factor inasmuch as a significant number of patients declined to participate in our study. In addition to causing asthma exacerbations, crack cocaine use has a number of other pulmonary complications associated with its use: acute respiratory symptoms, thermal airway injury, deterioration in lung function, pneumothorax and pneumomediastinum, bronchiolitis obliterans with organizing pneumonia, pulmonary hemorrhage, noncardiogenic pulmonary edema, pulmonary infiltrates with eosinophilia, and pulmonary vascular disease.10,18 –22 Inhalation of freebase cocaine has been shown to be associated with interstitial lung disease, with a reduction in diffusing capacity in some studies.20 The increase in prevalence of cocaine use in the United States may be an important factor responsible for increasing asthma severity and mortality, despite major advances in treatment modalities. Our study and others16,17 point to a relatively high prevalence of cocaine use among patients with asthma exacerbation, possibly contributing to the increase in asthma morbidity. An important implication of our study is to emphasize the importance for physicians to be alert to the possibility of crack cocaine as a precipitating factor for acute asthma. Improved access to health care and patient education, in addition to physician awareness of and adherence to NAEPP guidelines in treating asthma, are important factors in improving outcomes in asthma in this population. References 1 Leikauf GD, Kline S, Albert RE, et al. Evaluation of a possible association of urban air toxics and asthma. Environ Health Perspect 1995; 103:253–271 2 Lang DM, Polansky M. Patterns of asthma mortality in Philadelphia from 1969 to 1991. N Engl J Med 1994; 331:1542–1546 3 Waldbott GC. Asthma due to a local anesthetic. JAMA 1932; 99:1942 4 Rubin RB, Neugarten J. Cocaine-associated asthma. Am J Med 1990; 88:428 – 439 5 Rao AN, Polos PG, Walther FA. Crack abuse and asthma: a fatal combination. N Y State J Med 1990; 90:511–512 6 Rebuhn J. Association of asthma and freebase smoking. Ann Allergy 1988; 60:339 –342 7 Levenson T, Greenberger PA, Donoghue R, et al. Asthma deaths confounded by substance abuse. Chest 1996; 110:604 – 610 8 National Asthma Education Program. Expert panel report 2: Clinical Investigations
9 10 11 12
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guidelines for the diagnosis and management of asthma. Bethesda, MD: US Dept of Health and Human Services, National Heart, Lung, and Blood Institute; 1997. NIH publication 97– 4051 Cohen SG. Asthma among the famous: Nathan Tucker (1838 –1920), American physician. Allergy Asthma Proc 1997; 18:252–255 Haim DY, Lippmann ML, Goldberg SK, et al. The pulmonary complications of crack cocaine. Chest 1995; 107:233–240 Tashkin DP, Kleerup EC, Koyal SN, et al. Acute effects of inhaled and IV cocaine on airway dynamics. Chest 1996; 110:904 –910 Drug Abuse Warning Network. Semiannual Report: trend data through January-July 1988. Rockville, MD: US Dept of Health and Human Services, National Institute of Drug Abuse; 1989. DHHS publication ADM89 –1607 National Institute on Drug Abuse. Research report series: cocaine abuse and addiction 1999. Bethesda, MD: National Institutes of Health, 1999; NIH publication No. 99-4342 McNagny SE, Parker RM. High prevalence of recent cocaine use and the unreliability of patient self-report in an inner-city walk-in clinic. JAMA 1992; 267:1106 –1108
15 Rich JA, Singer DE. Cocaine-related symptoms in patients presenting to an urban emergency department. Ann Emerg Med 1991; 20:616 – 621 16 Osborn HM, Tang M, Bradley K, et al. New-onset bronchospasm or recrudescence of asthma associated with cocaine abuse. Acad Emerg Med 1997; 4:689 – 692 17 Gaeta TJ, Hammock R. Association between substance abuse and acute exacerbation of bronchial asthma [letter]. Acad Emerg Med 1996; 3:1170 –1172 18 Tashkin DP, Khalsa M, Gorelick D, et al. Pulmonary status of habitual cocaine smokers. Am Rev Respir Dis 1992; 145:92–100 19 Kissner DG, Lawrence WD, Selis JE, et al. Crack lung: pulmonary disease caused by cocaine abuse. Am Rev Respir Dis 1987; 136:1250 –1252 20 Albertson TE, Walby WF, Derlet RW. Stimulant-induced pulmonary toxicity. Chest 1995; 108:1140 –1149 21 Klinger JR, Bensadoun E, Corrao W. Pulmonary complications from alveolar accumulation of carbonaceous material in a cocaine smoker. Chest 1992; 101:1171–1173 22 Itkonen J, Schnoll S, Glassroth J. Pulmonary dysfunction in “freebase” cocaine users. Arch Intern Med 1984; 144:2195– 2197
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