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J. ©idlo, A. ©oral, J. Bauerová, S. Valko, B. Muráriková, J. Mlynár, *J. Valuch

Pulmonary macrophages in heroin addiction

Institute of Forensic Medicine, Slovak Postgradual Academy of Medicine and St. Cyril and Method‘s Hospital,

Head: Jiřina Bauerová, MD, PhD, Prof. assoc.

*Institute of Forensic Medicine, School of Medicine and Faculty Hospital, Comenius University, Bratislava, Slovakia

Head: Mirko Mego, MD, PhD, Prof. assoc.

Background: The pulmonary complications of illicit drug abuse may be the most common form of drug-induced lung disease. Main purpose: The aim of the study was to determine pulmonary complications associated with intravenous heroin abuse. Pacients and methods: Lung tissue samples from 43 drug addicts and 28 "normal" persons submitted for medico-legal autopsy at the Institute of Forensic Medicine of Slovak Postgradual Academy of Medicine and Institute of Forensic Medicine of School of Medicine of the Comenius University in Bratislava were evaluated by method of light microscopy. Results: In the heroin addict cases pulmonary oedema in 49% and emphysema in 7% of cases were found. Statisticaly significant (p > 0,05) increased number of hemosiderin-negative pulmonary macrophages in 88% of cases of drug addicts was found. Conclusions: The Increased number of pulmonary macrophages in the group of heroin addicts can indicate may lung defense mechanism defects and/or direct heroin influence on macrophages as well. The possible conclusion of this study for practical application: occurrence of increased number of hemosiderin-negative pulmonary macrophages by negative autopsy findings in young people points to the probability of heroin abuse as well as for the necessity to investigate option this in a person's history.
Key words: heroin addiction, morphology, pulmonary macrophages

Introduction
The prevalence of drug abuse is thought to be increasing in Slovak Republic in last ten years (Novomeský, 1996). The patterns of drug abuse prevalent in a given population are determined by a variety of factors such as the cost or availability of particular substances, peer pressure, local customs, and legal pressures. The pulmonary complications of illicit drug abuse may be the most common form of drug-induced lung disease (Rosenow et al., 1992). The potential for respiratory system complications depends not only on the drug used but also on the route of administration, the origin of the drug, the presence of contaminants, whether or not there is sharing of paraphernalia, and the host response of the individual user (Glassroth et al., 1987).
Worldwide, heroin is the most common substance taken by intravenous drug abusers (Hind, 1990). Heroin is usualy acetylated from the parent compound morphine and arrives in a pure form as a white powder. Pure heroin is rogressively adulterated ("cut") by diluting it 20- to 100 fold with soluble "fillers" such as quinine, lactose, maltose, mannitol, baking soda, starch, barbiturates, and chloroquine (O'Gorman et al., 1987). The concentration of heroin in the product sold to the user by the pusher varies from 0 to 20 percent. The user mixes the dry white powder in unsterile water or in saliva. The mixture is heated in a spoon or bottle cap held over a lighted flame and removed from the heat as soon as bubbles appear. Other forms of heroin such as "brown" heroin are poorly soluble in water and require acidification with substances such as lemon juice or vinegar before heating. The heroin mixture is aspirated into a syringe through a ball of cotton wool to filter out the larger impurities. The intravenous injection ("mainlining") is performed without sterilization of the skin, often in the presence of other users, who then share the syringe and needle without sterilization (Hind, 1990).
Intravenous drug abusers are at risk from infection and a wide range of lung parenchymal and vascular lesions unrelated to infection (tab. I), because the lung plays a very important role also in filtering foreign material entering the blood stream from an intravenous drug injection.
Patients and methods
Lung tissue samples from 43 drug addicts and 28 "normal" persons submitted for medico-legal autopsy at the Institute of Forensic Medicine of Slovak Postgradual Academy of Medicine and Institute of Forensic Medicine of School of Medicine of The Comenius University in Bratislava were fixed in formalin, processed by routine method and embedded in paraffin. Sections were stained with hematoxylin-eosin and Perl‘s reaction for evidence of hemosiderin and evaluated by method of light microscopy. Besides morphological findings described in the literature (tab. I) the presence of pulmonary macrophages (Fig. 1) was evaluated. The characteristics of both groups studied are included in table II. The control group was comprised above all of motor vehicle accident victims. The data obtained was statistically evaluated by means of Chi-quadrat test for table 2x2. The qualitative detection of morphine as a metabolite of heroin in the urine samples obtained by autopsy by means of latex agglutination immunoassay technique (ONTRAK) were tested. The concentration of opiates and their metabolites in urine samples by means of semi-quantitative fluorescence polarisation immunoassay technology (Abbott) was detected.
Results
In the group of intravenous heroin abusers of all pulmonary complications (tab. I) only parenchymal lesions as pulmonary oedema connected with intraalveolar bleeding in 21 of 43 cases i.e. 49 percent and emphysema in 3 of 43 cases i.e. 7 percent were found. Statisticaly significant (p > 0,05) increased number of hemosiderin-negative pulmonary macrophages (Fig. 2) in 38 of 43 cases of heroin addicts i.e. 88 percent compared with 11 of 28 cases i.e. 39 percent in control group (tab. III) was found. In the group of heroin addicts toxicological investigation of urine in 41 of 43 cases i.e. in 95 percent was performed. The presence of opiates and their metabolites in all of cases examined was found. Two patients survived for some days and toxicological investigation by autopsy was not necessary.
 
Table I. Pulmonary complications associated with intravenous drug abuse (Hasleton, 1996).

Infections

Human Immunodeficiency Virus

Pneumonia

Community Acquired

Aspiration

Septic Pulmonary Emboli

Fungal

Lung Abscess

Tuberculosis

Vascular Lesions

Foreign Body Embolism

Talc

Microcrystalline Cellulose

Cornstarch

Cotton

Mercury

Needles

Pulmonary Artery Medial Hypertrophy

Mycotic Aneurysm

Parenchymal Lesions

Pulmonary Oedema

Progressive Massive Fibrosis

Emphysema

Interstitial Pneumonia/Fibrosis

Hemosiderosis

 
Table II. Characteristics of analysed groups.
 

 

group of addicts

 

control group

No. Cases

43

28

Age (years)

17-43

15-29

Age average

21

21

 
Table III. Occurrence of pulmonary macrophages.

Pulmonary

Group of addicts

Control group

Macrophages

No.

No.

Fe Negative

Cases

%

Cases

%

Resent

38

88

11

39

Absent

5

12

17

61

Discussion and conclusions
Morphological changes in drug addicts forms a relatively new chapter in our daily morphological practice. The number of drug addicts in our country is relatively smaller and time of drug abuse is relatively shorter compared with western countries. The organism and individual organ injury to a great extent are known only from literature. The aim of our study was to determine histopathological findings in the lung of heroin addicts.
Heroin produces its effect by acting on several systems such as: central nervous system, cardiovascular system, respiratory system, gastrointestinal tract, urinary tract and reproductive system. The object of our interest is the effect of heroin on the respiratory system, where causes respiratory rate decrease, respiratory volume decrease, cough reflex inhibition, cilia movement inhibition and histamine release (Wenke, 1990).
From all pulmonary complications described in the literature in our work only parenchymal lesions as pulmonary oedema connected with intraalveolar bleeding in 49 percent of cases and pulmonary emphysema in 7 percent of cases in the group of heroin addicts were found. In the same group a very interesting finding such as increased number of hemosiderin-negative pulmonary macrophages in 88 percent of cases was found. This finding was statisticaly significant (p > 0,05) compared with the control group.
An increased number of pulmonary macrophages in 31 years old female, heroin addict with a 10 year addiction history, reported Magnan et al. (1991). Direct effect of morphine as a metabolite of heroin on macrophages in vitro by Singhal et al. (1993, 1996) was described. An increase in the percentage and absolute number of macrophages in lymphoid organs and in the spleen after long-term morphine administration to retrovirus-infected mice was found (Lopez et al., 1993). The possibility of direct propagation of pulmonary macrophages in the lung is mentioned by Ferenčík et al. (1999).
Based on this literary data we can assume, that an increased number of pulmonary macrophages in the group of heroin addicts with intravenous administration of heroin may indicate lung defense mechanism defects and/or direct heroin influence on macrophages as well.
The possible conclusion of this study for practical application is as follows: occurrence of increased number of hemosiderin-negative pulmonary macrophages by negative autopsy findings in young people points to the probability of heroin abuse as well as to the necessity to investigate this option in a person's history.
Acknowledgement
The authors wish to thank to Mr. P. Fiala MD, PhD from Institute of Forensic Medicine of School of Medicine of The Comenius University in Bratislava for kindly lending histological slides from 17 necroptic cases of heroin addicts.
References:
1. Ferenčík, M., Rovenský, J., Nyulassy, ©.: Imunológia. Základné termíny a definície. Bratislava, Slovak academic press, 1999, p. 283. -2. Glassroth, J., Adams, G., D., Schnoll, S.: The impact of substance abuse on the respiratory system. Chest, 91, 1987, p. 596-602. -3. Hasleton, P., S.: Spencer's pathology of the lung. New York, The McGraw-Hill companies, 1996, p. 1283. -4. Hind, C., R., K.: Pulmonary complications of intravenous drug abuse. 1. Epidemiology and non-infective complications. Thorax, 45, 1990, p. 891-898. -5. Lopez, M., C., Chen, G., J., Colombo, L., L., Huang, D., S., Darban, H., R., Watzl, B., Watson, R., R.: Spleen and thymus cell subsets modified by long-term morphine administration and murine AIDS - II. Int. J. Immunopharmacol., 15, 1993, p. 909-918. -6. Magnan, A., Ottomani, A., Garbe, L., Arnaud, A., Manelli, J., C.: Respiratory failure in a HIV seropositive heroin addict female. Ann. Fr. Anesth. Reanim., 10, 1991, p. 74-76. -7. Novomeský, F.: Drogy. História, medicína, právo. Martin, Advent Orion, 1996, p. 120. -8. O'Gorman, P., Patel, S., Notcutt, S., Wicking, J.: Adulteration of "street" heroin with chloroquine. Lancet, 1, 1987, p. 746. -9. Rosenow, E., C., III., Myers, J., L., Swensen, S., J., Pisani, R., J.: Drug-induced pulmonary disease. An update. Chest, 102, 1992, p. 239-250. -10. Singhal, P., C., Mattana, J., Garg, P., Arya, M., Shan, Y., Gibbons, N., Franki, N.: Kidney Int., 49, 1996, p. 94-102. -11. Singhal, P., C., Pan, C., Gibbons, N.: Effect of morphine on uptake of immunoglobulin G complexes by mesangial cells and macrophages. Am. J. Physiol., 264, 1993, p. F859-866. -12. Wenke, M. a spol.: Farmakologie. Praha, Avicenum, 1990, p. 600.
 
Correspondence to Jozef ©idlo, MD, PhD., Institute of Forensic Medicine, Slovak Postgradual Academy of Medicine and St. Cyril‘s and Method‘s Hospital, Antolská 11, 851 07 Bratislava, Slovak Republic
 
 
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