Background

The detection of drug-induced pulmonary and cardiovascular disorders is a significant challenge for physicians and radiologists.

Cocaine is the illicit drug most frequently encountered by patients in hospital emergency departments and is the leading cause of drug-related deaths reported by forensic physicians [1].

The pulmonary effects of cocaine may vary depending on the mode of administration, dosage, and the presence of other substances such as heroin or talcum powder. These effects include a range of complications including acute respiratory symptoms, barotrauma, airway damage, asthma, pulmonary edema, hemoptysis, and pulmonary hemorrhage [2]. “Crack lung” and eosinophilic lung disease, organized pneumonia, and bronchiolitis are also observed [3]. The clinical presentations of these conditions are varied and range from a dry cough to acute respiratory distress syndrome (ARDS) with lung failure, regardless of the duration and frequency of consumption [4].

Cocaine is available in four forms: hydrochloride salt, “freebase,” and crack, which is the most potent and addictive form of cocaine. The hydrochloride form of cocaine appears as a fine white powder; it is usually taken intranasally [5].

Freebase and crack cocaine have identical chemical compositions but differ in their characteristics and production methods [5]. Free-base cocaine is obtained by dissolving cocaine hydrochloride in water, followed by the addition of a base such as ammonia and a solvent such as ether or alcohol. In contrast, crack cocaine is formed by dissolving cocaine hydrochloride in water mixed with sodium bicarbonate (baking soda), which removes the hydrochloride and stabilizes the substance for heating. This process produces solid masses or ‘rocks’ of cocaine base, which become malleable when dried and can be smoked as they vaporize at high temperatures.

In 2021, an analysis conducted by the EU-funded EUSEME project examined the municipal wastewater of 13 European cities, revealing the presence of crack residues in all towns on every sampling day, with the highest levels detected in Amsterdam and Antwerp [6].

Respiratory symptoms are commonly observed following exposure to cocaine, especially after inhalation of crack cocaine combustion products [2, 7]. The particles generated during smoking are typically small, with an average size of 2.3 μm, facilitating their deposition in the alveolar region of the lung [8]. In addition, the smoking process produces a dark, tarry residue, which is often collected and smoked together with crack. The inhalation of these impurities leads to a significant accumulation of intracellular (macrophages) and extracellular carbonaceous pigment [9].

The term ‘Crack lung’ describes an acute syndrome characterized by diffuse alveolar damage and hemorrhagic alveolitis, occurring within 48 h of smoking freebase cocaine. It is attributed to prolonged inflammatory pulmonary injury and is associated with symptoms such as fever, hypoxemia, hemoptysis, respiratory failure, and diffuse alveolar infiltrates [10].

In this article, we will describe two cases of crack lung.

Cases

A 29-year-old patient was admitted to our emergency department (DEA) in a state of coma. Rescuers reported finding traces of drug use and blister packs of Lorazepam and Paracetamol at home. The EGA performed on admission to the Emergency room found metabolic acidosis (pH 6.67) and hyperglycemia (Glu 659 mg/dl). A treatment for diabetic ketoacidosis was started.

A total body Computed Tomography (CT) was performed. Abdominal findings were negative. CT scan of the thorax showed bilaterally, subpleural, and peri-hilar lung parenchyma, extensive areas of ground-glass parenchymal hyperdensity, with crazy pitting aspects, with relative sparing of the apices. No pleural effusion. (Figs. 1, 2). Sars-Cov-2 PCR swab was performed with a negative result.

Fig. 1
figure 1

Bilateral ground-glass opacities with subpleural and perihilar distribution with thickening of the septa (‘crazy paving’)

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Fig. 2
figure 2

Apical sparing (a). Absence of pleural effusion (b)

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Supportive therapy and corticosteroids were administered, but the patient progressed to ARDS within 24 h. Another High-Resolution Computed Tomography (HRCT) scan was performed, which shows consolidated, ground-glass confluent parenchymal opacities, with patchy distribution in the lower lobes and declivous portions of the upper lobes (Fig. 3).

Fig. 3
figure 3

Consolidated and ground-glass parenchymal opacities, with patchy distribution in the lower lobes and declivous portions of the upper lobes

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A 34-year-old male was brought to the DEA for vomiting and reported alcohol and drug intake. He was a diabetic patient who reported not having taken insulin therapy for several days. The EGA showed severe metabolic acidosis (pH 6.98; pCO2 12 mmHg; HCO3- 7.4). He had hyperglycemia and normal spO2 (100%). A whole-body CT scan with a contrast medium was performed. Chest scans showed bilateral ground-glass opacities with “crazy paving” appeareance, more represented at the lower lobes (Figs. 4, 5). Sars-Cov-2 PCR swab was negative. The broncho-alveolar lavage (BAL), performed during hospitalization, showed marked eosinophilia (> 40%). Supportive therapy and corticosteroids are administered, and within 72 h opacities at CT scan were resolved.

Fig. 4
figure 4

Bilateral ground-glass opacities with subpleural and perihilar distribution with ‘crazy paving’ appeareance

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Fig. 5
figure 5

Apical sparing (a). Absence of pleural effusion (b)

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Discussion

It is important to include drug abuse and crack lung in the differential diagnosis of acute respiratory symptoms with ground-glass opacities, as they are not uncommon in emergency departments and may rapidly progress to ARDS [4]. CT scan results are not specific, but it is important to carefully gather anamnestic data and to work together with the clinitians to reach a diagnosis and establish appropriate therapy.

Due to the presence of bilateral ground-glass opacities with crazy paving appearance, differential diagnosis in the presented cases included Sars-COV2 infection [11], which was excluded by the negative PCR swab.

Pneumocystis jiroveci pneumonia (PJP) is characterized by a CT pattern with ground glass opacities and interstitial thickening with crazy paving appearance predominantly involving perihilar or mid zones [12]: it was excluded due to the lack of documented immunodeficiency, negative autoantibody testing and absence of Pneumocystis jirovecii in bronchoalveolar lavage (BAL).

Other etiological agents causing interstitial pneumonia were excluded by bronchoalveolar lavage and microbiological tests.

Hypersensitivity pneumonitis with acute presentation was ruled out due to the absence of a history documenting exposure to allergenic agents and the non-typical CT pattern. The typical computed tomography (CT) manifestations of non-fibrotic HP reflect the presence of inflammatory cells around the bronchiole seen in histopathology. This leads to small, ill-defined ground-glass nodules with a profuse and uniform distribution across all lung zones with a preference for medium-upper zones [13].

Also organizing pneumonia can be included in differential diagnosis: Patel RC et al. reported respiratory failure with bronchiolitis obliterans with organized pneumonia documented at open lung biopsy has been reported in young crack cocaine smokers [14]. Although there is no strict definition of organizing pneumonia CT presentation, the characteristic pattern of this disease could be considered to include patchy consolidations and ground-glass opacities with a peri-lobular distribution. Halo sign or reverse Halo sign may appear [15].

In the reported cases, the temporal relationship between the appearance of the bilateral opacities, the history documenting drug use, and the onset of hypoxemia suggests the diagnosis of "Crack lung", as described by Gotway et al. who defined crack lung as the development of respiratory failure with increased opacity in bilateral airspace areas that appears shortly after crack use and clears rapidly after its cessation [16]. Crack use induces ischemia of pneumocytes by the following phenomena: thermal damage to the airways, direct toxicity, inflammatory damage, barotrauma, and vasospasm [12]. Diffuse alveolar damage and alveolar hemorrhage with eosinophilic cell infiltration and IgE deposits are found in the lung tissue [13].

Crack lung may have many manifestations at Chest HRCT scan.

Pulmonary eosinophilia linked to cocaine inhalation is widely recognized and reported in cases of crack lung and other forms of eosinophilic lung disease induced by cocaine [17, 18]. Affected individuals typically exhibit pulmonary eosinophilia in BAL and varying levels of peripheral eosinophilia, with eosinophils accounting for up to 40% of the total white blood cell count [18, 19]. In our reported cases, BAL confirmed the presence of eosinophiles > 40%.

Imaging findings range from predominantly interstitial and perihilar opacities (as shown in Figs. 1, 4) to a more alveolar presentation characterized by airspace consolidation, often with a patchy, randomly distributed pattern or peripheral predominance [20]. Crazy paving appearance may be present (as shown in Figs. 1, 4), while pleural effusion and apical involvement are uncommon (as shown in Figs. 2, 5) [11]. Short-term exposure to cocaine can trigger intense bursts of acute inflammatory activity by activating polymorphonuclear neutrophils, leading to the production of interleukin 8 [21].

Strong DH et al. report eosinophilic “empyema” alongside eosinophilic pneumonitis resulting from crack cocaine smoking, accompanied by peripheral eosinophilia and eosinophils in pleural fluid [22].

Cocaine is also the most common toxic cause of acute diffuse pulmonary hemorrhage [23]. Occult pulmonary hemorrhage is most common, but it may also present with hemoptysis. Cocaine abuse can mimic primary systemic vasculitis and can induce vasculitic disorders such as Churg-Strauss syndrome or Goodpasture’s syndrome, which can lead to pulmonary hemorrhage [24]. McGrath et al. reported that cocaine alone induces autoimmunity, especially when combined with levamisole, a chemotherapeutic agent no longer in use, but which is used as a cocaine adulterant or bulking agent [25].

On high-resolution computed tomography (HRCT), pulmonary hemorrhage often presents as ground-glass opacities, which may be accompanied by interlobular septal thickening, resembling a “crazy-paving” pattern [26]. Additionally, centrilobular nodules, sometimes with a tree-in-bud pattern, may also be observed [24]. Since pulmonary hemorrhage and eosinophilic disease may be radiographically indistinguishable, we globally use the term “crack lung” to describe this scenario [20].

Moreover, cardiogenic and noncardiogenic pulmonary edema has been reported in association with intravenous cocaine abuse and crack cocaine smoking [10].

Another well-recognized complication of both crack cocaine smoking and powdered cocaine inhalation is barotrauma, which can present as pneumothorax, pneumomediastinum, pneumopericardium, or subcutaneous emphysema. Kloss B et al. report that cocaine users increase pressure after smoking, typically doing forceful coughing to enhance drug absorption and maximize its effect [27].

Chronic cocaine use can lead to the development of interstitial diseases, pulmonary hypertension, and tumors [10].

Treatment in cases of crack lung is supportive therapy and withdrawal. A response to corticosteroids has been reported in some cases [16]. In our described cases, a Chest X-ray was performed after administration of corticosteroids and showed the disappearance of parenchymal opacities.

Conclusions

Understanding the pleuropulmonary complications linked to illicit drug abuse is crucial for radiologists. The crack lung is one of the wide ranges of manifestations in cocaine abuse. Given the serious medical and social implications of drug abuse, radiologists play a pivotal role in the early detection and management of these conditions.