Cannabinoids Identification in Lung Tissues of Young Cannabis Smokers Operated for Primary Spontaneous Pneumothorax and Correlation with Pathologic Findings
Mario Bisconti, Giuseppe Marulli, Roberta Pacifici, Francesco Sollitto, Giulia Nex, Xenia Trabucco, Nicoletta Pia Ardò, Maria Concetta Rotolo, Giulia De Iaco, Teodora Panza, Debora Brascia, Marcella Schiavone, Francesca Signore, Francesco Pistelli, Angela De Palma
Respiration, 2019.
Doi : 10.1159/000503456
Abstract
Background : Several studies suggested the association between tobacco and cannabis smoking and the risk of primary spontaneous pneumothorax (PSP), but none demonstrated cannabinoids in human lung tissues.
Objectives : The aim of this study was to identify cannabinoids in lung specimens of young cannabis smokers, operated for PSP, and investigate on their pathologic findings, to determine the role of cannabis in PSP pathogenesis.
Method : A prospective, multicenter study was conducted, enrolling patients admitted for PSP. Inclusion criteria were PSP requiring surgical treatment and history of cannabis smoking, associated or not to tobacco. Control cases were nonsmokers, and tobacco only smokers operated for PSP. Lung apex wedge resection by video-assisted thoracic surgery was performed. Two lung specimens, for pathological and toxicological examination, were taken from each patient.
Results : Twenty-nine male patients were enrolled: 21 (72.4%) tobacco and cannabis smokers, 2 (7%) cannabis only smokers, 3 (10.3%) tobacco only smokers, 3 (10.3%) nonsmokers; all underwent lung apicectomy, 4 bilateral surgery, for a total of 33 procedures. Typical PSP pathologic findings were mainly detected in control cases, other alterations in cannabis users. Lung specimens resulted positive for cannabinoids on 22/33 cases (19/22 reported being, 3/22 not being cannabis smokers), negative on 11/33 (3/11 reported not being, 7/11 having been cannabis smokers, 1/11 cannabis smoker).
Conclusions : Our study demonstrated the presence of cannabinoids and particular pathologic alterations in lung tissues of young cannabis smokers with PSP, supporting the correlation between this disease and marijuana abuse and suggesting spontaneous pneumothorax “secondary to marijuana” as a new nosological entity.
Keywords : Primary spontaneous pneumothorax · Cannabis · Smoking · Lung · Cannabinoids · Tetrahydrocannabinol
Introduction
Cannabis smoke is nowadays very common among young people in the Western world [1]. In the last few
years, some Authors have highlighted the deleterious effects of tobacco and cannabis consumption on the respiratory system [2], and several studies and case series suggested the possible association between smoking tobacco and cannabis and the risk of developing pulmonary bullous dystrophy and primary spontaneous pneumothorax (PSP) [3–6]. This correlation leads to the consequent hypothesis of cannabis acting as the cause of a spontaneous pneumothorax in fact “secondary” to marijuana smoking [7], which should therefore be considered and classified as a new nosological entity among the different types of
pneumothorax.
Moreover, some Authors have recently showed experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and lung emphysema in an animal model [8]. However, to the best of our knowledge, nobody has demonstrated or identified cannabinoids in human lung tissues and investigated about their direct role in the pathogenesis of PSP in a human model.
The aim of this study was to identify and determine the presence of the principal cannabinoid, delta-9-tetrahydrocannabinol (THC), and its metabolites, cannabinol (CBN) and cannabidiol (CBD), in human lung specimens, collected from a group of young, otherwise healthy patients hospitalized and operated for PSP and former or current tobacco smokers with a history of cannabis consumption; a group of nonsmokers and of tobacco only smokers was used as control group for comparison. Correlation with the presence of lung bullous disease and other alterations at pathological examination in the different
groups was also investigated, in order to determine the possible role of cannabis in the pathogenesis of pneumothorax.
Materials and Methods
This is a prospective, multicenter study, enrolling patients admitted in 2 Sections of Thoracic Surgery with a diagnosis of PSP from February 2017 to April 2018.
Inclusion criteria in the study were PSP requiring surgical treatment (persistent pneumothorax after chest tube insertion or with chest computed tomography evidence of lung bullous idiopathic dystrophy or recurrent pneumothorax) and history of cannabis smoking, associated or not to tobacco smoking. Control cases were represented by a group of nonsmokers and a group of tobacco only smokers, both operated for PSP during the same period.
At admittance, medical history was carefully collected, and subjects were screened for eligibility if they were tobacco smokers and/or drugs addicts (marijuana, cocaine, opiates, others), and it was investigated the way of administration and the time between the last administration and the first appearance of pneumothorax symptoms (chest pain, cough, dyspnea).
Surgical treatment of pneumothorax consisted in a wedge resection of the lung apex (“apicectomy,” including apical blebs and/ or bullous dystrophy) with endoscopic staplers and pleurodesis by video-assisted thoracic surgery; sometimes evident blebs in other lobes were resected, too.
In addition to the standard surgery consent, a written informed consent was obtained from each patient for pathological and toxicological examination of pleuro-pulmonary tissue.
Two specimens were taken from each patient: one sent to our University Hospital Division of Pathology for standard pathological examination and the second, frozen (–18 ° C), to the National Centre on Addiction and Doping of the “Istituto Superiore di Sanità” in Rome for toxicological examination and identification of cannabinoids in lung tissue (Appendix). The identification of cannabinoids was carried out blindly.
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