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
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)
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
Human Immunodeficiency Virus
Septic Pulmonary Emboli
Foreign Body Embolism
Pulmonary Artery Medial Hypertrophy
Progressive Massive Fibrosis
Table II. Characteristics of analysed groups.
group of addicts
Table III. Occurrence of pulmonary macrophages.
Group of addicts
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.
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.
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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