Primary Spontaneous Pneumothorax in Cannabis Smokers - Distinct Clinical Features and Challenging Management

Background: Cannabis use had been increasing Worldwide, especially in our developing countries. It had been associated with a higher risk of a primary spontaneous pneumothorax (PSP) occurrence and recurrence. This study aimed to highlight the main clinical and radiological features as well as the outcomes of Cannabis smokers with a PSP.

Methods: We conducted a retrospective, analytical study including patients admitted for a primary spontaneous pneumothorax in our department of Pneumology between January 2018 and December 2022. They were divided into two groups: cannabis smokers (G1) and non-smokers (G2).

Results: We included 183 patients with a mean age of 30 years. We noticed a male predominance (99.5%). Most of them were tobacco smokers (95.1%) with an average of 14.4 packs per year. About half of them were cannabis-smokers (44.3%). The patients in the first group (G1) were younger (p=0.026). They were taller (p=0.008) with a more marked slender silhouette (p=0.04). They had a lower socioeconomic level (p=0.005). They reported a mean Cannabis usage of 1.7 joints/day. Dyspnea was more commonly noticed among them (p=0.03). Apical blebs (p=0.018) and bullae (p=0.045) were more frequent in these cases. The chest drainage (p=0.036) and the hospital stay (p=0.047) durations were longer in the first group. The PSP recurrence rate was higher in the same group with a mean of 1.3, without any significant difference (p=0.29). The PSP was more often total (p=0.037) and associated with apical blebs (p=0.048) after the first recurrence in G1. The postoperative air leak (p=0.037) and the hospital stay (p=0.009) durations were also longer among these cannabis-smokers.

Conclusion: We underlined that Cannabis use may contribute to apical bullous formation and emphysema, leading to an increased risk of a primary spontaneous pneumothorax with a more challenging management.

Cannabis use had been increasing worldwide over the past Century, especially in our developing countries [1], commonly known as (“Hachich” or “Zatla”), particularly among children and young adults, mainly due to the public growing support for its legalization and its perceived safety [2,3]. It is the most used illicit drug and the second most smoked substance after Tobacco [3,4]. A recent study reported Cannabis usage in about 209 million People in the World, with a 23% increase since 2010[3]. The Cannabis consumption was noticed in about 8% of Tunisian students in 2021 [2]. Cannabis had been associated with a wide spectrum cardiovascular (myocardial infarction, arrhythmias, heart failure …), pulmonary (Chronic Bronchitis, Pneumothorax, hypersensitivity Pneumonitis…), psychiatric (anxiety, delirium, psychosis, schizophrenia…) and neurological (Cerebral ischemic strokes, Alzeihmer, Parkinson…) diseases [5-7].

The Cannabis smoke contains more than 500 identified harmful chemical substances, with about 125 phytocannabinoids, which are the main psychoactive substances responsible for its physical and psychological effects. Recent studies suggested that this drug may lead to macroscopic and microscopic lung changes with bullae formation, which rupture may lead to a primary spontaneous pneumothorax (PSP). This study aimed to compare the clinical and radiological features, management strategy, outcomes, and recurrence rates of a primary spontaneous pneumothorax (PSP) between cannabis-smoking and non-cannabis-smoking patients and to evaluate the association between cannabis use and the disease severity, including bullous formation, postoperative complications as well as the treatment challenges.

We conducted a retrospective, observational, comparative and analytical study including patients aged more than 15 years; admitted in our department of Pneumology for a primary spontaneous pneumothorax (PSP); between January 2018 and December 2022 in collaboration with the Chest Surgery department. The patients hospitalized for a secondary, iatrogenic or traumatic pneumothorax had been excluded. The included patients were divided in two groups according to their cannabis consumption. The first group (G1) included cannabis smokers (observational group). Whereas, the second group (G2) was composed of non-cannabis-smokers admitted for PSP (control group).

The included cases had a thorough clinical examination, a Chest X-ray, a Chest CT scan, blood tests, and an electrocardiogram. A medical surveillance was considered in partial asymptomatic and well-tolerated primary spontaneous pneumothorax. Chest drainage was performed in the case of a total or a symptomatic PSP. The main Chest surgery indications were the thoracic drainage failure, bilateral pneumothorax, hemothorax, the first contralateral recurrent or the second ipsilateral pneumothorax, according to the British Thoracic Society (BTS) Guidelines [8]. The patients underwent a video-assisted thoracoscopic (VATS) surgery. They had a mechanical abrasion and a chemical pleurodesis. A stapled bulbectomy was also performed in the case of bullae.

Ethical Approval

The ethical committee of our Charles Nicolle hospital approved our clinical study (decision approval number: FWA 00032748/ IORG 0011243). An informed consent was obtained from the patients for their clinical, radiological and biological findings publication.

Statistical Analysis and Data Management

The results were collected in an electronic database. We used a recent SPSS (Statistical Package for Social Science) version 27 for the data analysis. The normality of the variables was tested using the «Ghauss Test». The numerical variables were represented as means, medians and standard-deviations (SD). Concerning the normally-distributed continuous variables, the differences between the groups were assessed using the «Student’s T-Test». The correlations between the variables were analyzed using the Spearman and the Pearson tests.

We included 183 patients, mainly of men (99.5%). About half of the patients (44.3%) were included in the observational group. The Cannabis smokers were significantly younger (p=0.026). They were taller (p=0.04) with a more pronounced slender silhouette (p=0.008). They reported a mean Cannabis consumption of 1.7 joints/day with a mean duration of 70.5 months (ranging from 5 months up to 216 months). Only 15 patients (18.5%) had already stopped cannabis use, with a mean weaning duration of 24.6 months. Among which, a Cannabis-withdrawal syndrome was noticed in 56 cannabis users (69.1%). A concomitant Tobacco smoking was reported in almost all the patients (95.1%) in G1 (p = 0.04), with a mean cigarette smoke of 14.4 pack-year (ranging from 1 pack-year up to 60 pack-year). Among which, 18 patients (10.4%) had already quit Tobacco smoking.

Regarding the clinical findings, dyspnea was more commonly reported in the first group (54.3%) versus (38.2%) in the second group with (p=0.03), unlike the chest pain (97.1% versus 79.5%) with (p=0.84) and the dry cough (3.9% versus 4.9%) with (p=0.73), as shown in the first table above. Concerning the radiological features, the PSP was more often large among cannabis users during the first episode (p=0.05). The Chest CT scan revealed apical blebs or bullae in 20.8% of the included patients. It is worth mentioning that apical bullae (p = 0.018) and blebs (p = 0.045) were more frequent among cannabis-smokers.

Table 1: Main Patients clinical and radiological findings during the first episode of a primary spontaneous pneumothorax:

G: group, PSP: primary spontaneous pneumothorax, n: number, %: percentage, Kg: kilogram, cm: centimeter, m: meter.

During the first episode of PSP, a bed rest with a strict monitoring was considered in 11 cases (6%). A chest tube drainage was reported in about half of the included patients (56.3%). It was preceded by a needle aspiration in two patients (1.1%). The mean chest drainage duration was 6 days (ranging from 2 days up to 21 days). It was longer in cannabis users compared to the control group (p=0.036). A drainage failure was noticed in 65 cases (35.5%) and was more frequent in the first group (39.5%) versus (34.4%) in the second group, without any significant difference (p=0.4).

A Chest surgery was initially performed in just two patients (1.1%). Besides, 67 patients (36.6%) were operated on during the first episode, without any significant difference between both groups (p=0.51). The mean air leak duration was 4 days (ranging from 1 day up to 16 days), as shown in Table II. It was also longer in cannabis users, without any significant difference between the groups (p = 0.179). Concerning the intraoperative findings, the bullous lung lesions were reported in almost all the patients (92.5%). Apical bullae were more common in the first group (96.9%) compared to the second group (88.6%), without any significant difference (p=0.1). The mean hospital stay duration during the first episode was 7 days (ranging from 2 days up to 25 days). It was longer in cannabis smokers (7.68 days versus 6.48 days) with (p=0.047).

Table 2: Primary Spontaneous Pneumothorax First Episode Management and Follow-up:

G: group, n: number, %: percentage.

The pneumothorax recurrence occurred in about half of the included patients (42.6%), with a mean recurrence rate of 1.3. It was more frequent in cannabis smokers without any significant difference between both groups (p=0.29). The first PSP recurrence was more often total among the patients in the first group (p=0.037). Concerning the management of the recurrent PSP, a chest drainage followed by surgery was reported in 23 patients (29.5%). The Chest surgery was performed in 54 patients (69.2%). Just one patient had only a chest drainage. Concerning the intraoperative findings, apical bullae were noticed in almost all the patients (94.8%), mainly in the cannabis smokers (100%) (p= 0.048). The mean postoperative chest drainage duration was 3.95 days. It was longer in the first group (p=0.089). The mean postoperative air leak duration was 2.27 days. It was longer in the same group (p=0.037). The Cannabis users had more postoperative complications without any significant difference (p=0.1). Indeed, the patients had a higher incidence of postoperative prolonged air leak (p=0.064) and a longer hospital stay duration (p=0.009) in the observational group.

Table 3: Patients main findings during the First Recurrence of Primary Spontaneous Pneumothorax.

G: group, PSP: primary spontaneous pneumothorax, n: number, %: percentage.

Cannabis smoke had been associated with a greater risk of primary spontaneous pneumothorax (PSP). The underlying mechanisms remain misunderstood. It may lead to the lung bullous lesions formation (bullae, blebs…), which rupture may result in a PSP.  The direct toxicity of cannabis seems to play an important role. In fact, this drug contains more than 500 harmful chemical substances, mainly the phytocannabinoids [9,10]. Besides, a cannabis joint is equivalent to 3 to 4 cigarettes of Tobacco [9,11]. It may induce macroscopic and microscopic lung damage. The lung tissue histological exam findings in cannabis smokers revealed a marked inflammation with many pigmented macrophages and a squamous metaplasia [12-14]. Indeed, performing the Valsalva maneuver in order to increase the cannabinoid absorption may lead to a pneumothorax due to the increased pressure inside the bullae, causing their rupture [8,15]. In fact, Fiorelli and al. observed that cannabis-smokers had more bullous lesions than non-smokers (p less than 0.05) [16].

Similar studies had reported an increased prevalence of emphysematous and bullous lesions, mainly in the apical region, according to the chest CT scan findings in mixed cannabis and tobacco smokers compared to exclusive tobacco smokers. Another study conducted by Ruppert and al. in 2018 revealed that emphysema was noticed in half of the exclusive tobacco smokers versus 71.9% in mixed cannabis and tobacco smokers [9]. The same findings were reported in a study published by Chardon and al. about three cases of Cannabis users. They also noticed the presence of emphysematous and bullous lesions in the apical region [10,11]. Moreover, a review published by Underner and al. based on 13 cannabis smokers case reports with a PSP showed the same results [8]. Indeed, the emphysematous lesions were predominant among cannabis smokers, according to the intraoperative findings reported by Stefani and al. [12]. A similar study published by Bisconti and al. including 21 cannabis smokers operated on for a spontaneous pneumothorax revealed that those with positive toxicological tests for cannabinoids had more bullous lung lesions (93%vs 14%) with (p less than 0.001) [13].

It is worth mentioning that Cannabis smokers with a PSP had a more pronounced slender silhouette. In fact, their lungs were may be more stretched vertically, making the blebs or bullae more vulnerable to rupture, especially under pressure. Besides, larger puffs, deeper Cannabis inhalation with a more prolonged air retention compared to Tobacco could increase the contact time between this harmful drug and the bronchial mucosa. Indeed, this illicit drug intake may lead to an increased airways resistance leading to an air trapping with a greater alveolar pressure. These mechanisms seem to be the main contributing factors leading to a pneumothorax [7].

The Cannabis use had been more common among children and young adults. A comparative study published by Fiorelli and al. reported that mixed cannabis and tobacco smokers were younger than exclusive tobacco smokers (27.4 years versus 45 years) with (p less than 0.05) [16]. According to the World Drug Report, the annual cannabis use rate among teenagers was 5.34% in 2021 [17]. In addition, 6.3% of young adults aged between 18 years and 25 years used cannabis regularly in France [8]. The earlier cannabis smoking onset may also explain the early formation of bullae and emphysematous lesions which rupture may lead to a pneumothorax in these patients [18]. 

We still need clear recommendations regarding the management of a pulmonary spontaneous pneumothorax (PSP) in these Cannabis-smokers for a personalized approach. The chest drainage failure was more common among them, as reported by Chardon and al. [11]. The authors also noticed that the Chest drainage duration was longer in these patients (21 days versus 11 days). The same findings were also reported in our study. This complication is may be due to the more frequent bullous or emphysematous lesions in these cannabis smokers. However, the postoperative outcomes in cannabis-smokers were less documented in literature compared to Tobacco-smokers. It is worth mentioning that the postoperative air leak duration in Cannabis users (p = 0.037) as well as the chest drainage duration after surgery during a first recurrence were longer according to a study published by Stefani and al. [12]. Similar findings were reported by Hristova and al. with a higher rate of a persistent air leak in Cannabis-smokers compared to non-smokers (43.5% versus 6.2%) with (p=0.01) supporting our study results [19].

The Cannabis usage was associated with a higher recurrence rate of a primary spontaneous pneumothorax (PSP) compared to those due to the Tobacco smoke (54% versus 28%) with (p=0.014), according to a study conducted by Wakefield and al. [20]. Similarly, Stefani and al. reported that the postoperative PSP recurrence was more common among mixed Cannabis and Tobacco smokers compared to those who smoked tobacco alone (p=0.088) [12]. The same findings were also mentioned in our study. The PSP recurrence is may be due to a persistent exposure to cannabis and tobacco smoke. Besides, the cannabis users were more prone to develop bullous and emphysematous lung lesions, with a higher recurrence rate, especially if these lesions were not fully treated during the initial chest surgery procedure.

Our study suggested that cannabis use was associated with distinct clinical and radiological features in patients with a primary spontaneous pneumothorax (PSP). Cannabis use was linked to longer chest drainage and hospital stay durations and to a higher PSP recurrence rate. The management of PSP in cannabis users was more challenging, with a more prolonged postoperative air leak and complications. Further multicenter research studies are still required in order to better understand the underlying mechanisms in order to tailor a personalized approach. We do recommend the establishment of preventive strategies, including targeted educational programs for at-risk youth and cannabis smokers Finally, should we consider the Cannabis-induced spontaneous pneumothorax as primary or secondary given the frequent and extended bullous and emphysematous lesions?

Ethics Approval

We respected the 1964 Helsinki Declaration principles and the Committee of Publication Ethics (COPE) Guidelines. We obtained the Charles Nicolle Hospital Ethical Committee approval (decision approval number: FWA 00032748/ IORG 0011243). 

Consent to Participate

A written informed consent was obtained from all the patients. 

Publication Consent

All the authors confirmed that the patients provided a written informed consent for the publication of all their clinical, radiological and biological data.

Availability of Data and Materials 

The patients clinical, radiological, biological and histological findings used in this study are available. They can be requested from the corresponding author.

Competing Interests

All the authors declare that they don’t have any financial or non-financial interest to disclose.

Funding

The authors declare that no funds, grants, or other support had been received during the preparation of this manuscript.

Author Contributions

E. Ben Jemia: Conceptualisation, Methodology, Administration, Writing, Supervision, Review.

O. Ben Moussa: Methodology, Analysis and Visualization Writing, Review.

A. Saidane, M.S Boudaya, Y. Ben Attig, H. Hedhli, Haifa Zaibi, Jihen Ben Amar: Writing, Review.

All the authors participated in this manuscript writing and review. They had approved this final version.