COPD is the most common cause of SSP, with 50% to 70% of SSP cases attributed to COPD in small case series. Rupture of apical blebs or bullae is the usual cause. Patients with COPD may also be at higher risk for iatrogenic pneumothorax (e.g., venous catheterization, mechanical ventilation), particularly when there is a significant amount of underlying emphysema or air trapping. The severity of COPD correlates with the likelihood of developing SSP (Lee, 2021a).
Cystic Fibrosis (CF):
Approximately 3% to 4% of patients with CF will have an episode of SSP during their lifetime, but in those who survive to age 18, the incidence is 16% to 20% (Lee, 2021a). CF-related SSP is usually due to the rupture of apical subpleural cysts. The risk of pneumothorax in CF increases with the severity of lung function abnormalities. Other than cysts and fibrosis, other factors that may predispose to the development of pneumothorax in CF, which may reflect disease severity rather than being independent risk factors, include (Lee, 2021a):
- A prior episode of massive hemoptysis
- Infection with Aspergillus species
- Infection with Burkholderia cepacia complex
- Infection with Pseudomonas aeruginosa
- Noninvasive positive pressure
- Possibly inhaled medications
Both primary and metastatic lung malignancy has been associated with SSP. Among 168 patients with SSP, malignancy was the underlying cause in 16% (Lee, 2021a). The underlying malignancy was more commonly a lung primary than metastatic disease. Potential mechanisms include tumor necrosis, endobronchial obstruction with air trapping, development of necrotizing cysts or pneumonia, and coexisting COPD/emphysema.
Less commonly, malignancies that metastasize to the lung are associated with the development of necrotic cysts, which can result in SSP. Examples include (Lee, 2021a):
- Gastrointestinal adenocarcinoma
- Genitourinary adenocarcinoma
- Mesenchymal cystic hamartoma
- Pleuropulmonary blastoma
Necrotizing Lung Infections:
SSP can complicate the course of necrotizing pneumonia due to Pneumocystis jirovecii (i.e., pneumocystis pneumonitis [PCP]), TB, bacteria, and less often fungi or other microorganisms, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Lee, 2021a). The relative frequency of these etiologies depends upon the frequency of these diseases in the population studied. The presumed common mechanism underlying pneumothorax in patients with lung infection is direct invasion and necrosis of lung tissue, including the pleura by the microorganism itself.
Unilateral and bilateral SSP can be seen in patients with PCP, most often in human immune deficiency virus (HIV) patients. In the era of antiretroviral therapy (ART), the frequency of pneumothorax complicating PCP is approximately 5% to 10% (Lee, 2021a). However, another study reported lower rates, with pneumothorax complicating only 1.2% of all hospital admissions in a cohort of 599 HIV-infected patients. However, over half had non-pulmonary reasons for admission.
In patients with HIV-related PCP, it has been hypothesized that the administration of aerosolized pentamidine may increase the likelihood for PCP to grow and cause cavitation in the peripheral parts of the upper lobe, thereby increasing the risk for pneumothorax (Lee, 2021a). This phenomenon may relate to the preferential delivery of the aerosolized agent to the proximal parenchyma of the lower lobes rather than the upper lobes. Unlike bacterial pneumonia, pneumothorax associated with PCP is more likely to be bilateral than unilateral.
SSP has been associated with bacterial pneumonia caused by Staphylococcus, Klebsiella, Pseudomonas, Streptococcus pneumoniae, and anaerobic organisms. Among 168 patients with SSP, bacterial pneumonia was the etiology in 11% of cases (Lee, 2021a). SSP in bacterial pneumonia is more likely to be unilateral than bilateral. It can be associated with an extension of bacterial infection into the pleura and the development of empyema, giving the appearance of a hydropneumothorax.
SSP occurs in 1% to 3% of patients hospitalized with pulmonary TB (Lee, 2021a). Rates are higher in endemic areas. The pneumothorax is usually due to the rupture of a tuberculous cavity into the pleural space.
Other pulmonary infections have been associated with pneumothorax, including fungal, viral, and mycobacterial infections other than TB.
Cystic Lung Disorders:
Pneumothorax is common in lung conditions associated with cysts. However, since many of these conditions are rare, pneumothorax in this setting may masquerade as PSP when the underlying diagnosis is unknown. Disorders associated with cysts include conditions such as (Lee, 2021a):
- BHD syndrome
- Diffuse Langerhans cell histiocytosis
- Lymphocytic interstitial pneumonitis (e.g., Sjögren syndrome)
Catamenial pneumothorax refers to a pneumothorax occurring in association with menses due to thoracic endometriosis. Young females with endometriosis may experience menses-related pneumothoraces if pleural involvement exists. CP or hemoptysis perimenstrually in a young woman with or without a history of endometriosis might suggest catamenial pneumothorax (Lee, 2021a). In this condition, pneumothorax is thought to relate to the development and involution of pleural implants comprised of endometrial tissue. Consequently, some experts consider this PSP since parenchymal lung disease is typically absent.
Pneumothorax is seen in HIV due to several etiologies, particularly infections including (Lee, 2021a):
- Bacterial pneumonia
- Fungal, viral, and mycobacterial infections
- PCP pneumonia
- Pulmonary TB
Patients with HIV can also be at risk for iatrogenic pneumothorax and pneumothorax due to the presence of pneumatoceles (typically from old Staphylococcal or PCP infection), Kaposi sarcoma, intravenous drug abuse, and cigarette smoking. One report suggested that the degree of immunosuppression in HIV may affect the etiology of pneumothorax. In patients with CD4 positive lymphocyte counts >200 cells/mL, pneumothorax was more likely due to bacterial pneumonia, whereas pneumothorax was more often associated with those with counts <200 cells/mL Pneumocystis jirovecii (Lee, 2021a).
Architectural Abnormalities of the Pleural Membrane:
Pneumothorax may occur in conditions where the pleural membrane's integrity and parenchyma are abnormal, the diagnosis of which may or may not be known at the time of presentation. These include (Lee, 2021a):
- Ehlers-Danlos syndrome
- Marfan syndrome
In Marfan and Ehlers-Danlos syndrome, it is thought that abnormal elastin or collagen content of the pleural membrane and parenchyma may predispose patients to pneumothorax (Lee, 2021a). Why patients with homocystinuria develop pneumothorax is less clear, but homocysteine plays a role in vascular homeostasis and smooth muscle and collagen production regulation in the lung. Patients with Marfan syndrome may also develop parenchymal cysts that may increase the risk of developing a pneumothorax.
Other less common causes of SSP include:
- Ankylosing spondylitis
- Granulomatous lung diseases (e.g., rheumatoid arthritis, granulomatosis with polyangiitis, and sarcoidosis)
- Inhalation of cocaine
- Interstitial lung disease (e.g., idiopathic pulmonary fibrosis, silicosis)
- Several case series have also described pneumothorax occurring in patients with coronavirus disease 2019 (COVID-19) without noninvasive or invasive ventilation.