Diffuse cystic lung diseases (DCLDs) are a group of disorders with different mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In their new review, Cooley et al., 2017 give an overview of the epidemiology, clinical features, and management of spontaneous pneumothoraces in patients with DCLDs, with a focus on Birt-Hogg-Dube (BHD) syndrome, lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). The understanding of spontaneous pneumothoraces in DCLDs can help clinicians to find an early diagnosis and appropriately manage the disorders.
Patients with BHD have a 50-fold greater likelihood of spontaneous pneumothorax as compared with controls. Recently, studies have shown that BHD can be the underlying cause of 5–10% of apparent primary spontaneous pneumothoraces (Johannesma et al., 2015). The prevalence of spontaneous pneumothorax in BHD varies between reports. Pneumothorax prevalence rates of 22.5-38% are reported by renal/skin-focused centres, while prevalence rates of 42–76% are reported from patients in pulmonary cohorts. Pneumothoraces due to BHD usually occur in the patient’s mid-late 30s; however, they have been reported in pediatric and geriatric patients. Lung cysts and cyst burden are associated with increased risk of pneumothorax. Interestingly, there are reports of pneumothorax in patients without apparent cysts on CT imaging. Family history of pneumothorax is associated with higher risk of pneumothorax but smoking and the presence or severity of renal tumours or fibrofolliculomas are not. Pneumothorax recurrence rates in BHD are estimated to be 75–80%. Patients with BHD-associated pneumothorax experience an average of 3.6 total episodes of pneumothorax. Given the high recurrence rate, pleurodesis should be performed following the first pneumothorax rather than waiting for a recurrence since pleurodesis can halve the recurrence rates of ipsilateral pneumothorax in BHD patients.
55–73% of patients with LAM experience a pneumothorax in their lifetime, with pneumothorax leading to the diagnosis of LAM in approximately 40% of patients. On average, patients experience 2.2 pneumothoraces before the diagnosis of LAM is made. Patients with larger cyst size on HRCT and those with a history of smoking are more likely to develop a pneumothorax. Given the high rates of recurrence, pleurodesis should be performed after the first spontaneous pneumothorax in patients with LAM. In one study, the ipsilateral pneumothorax recurrence rate was 66% if managed conservatively, but this was reduced to 27% with chemical pleurodesis and 32% with surgical pleurodesis.
Approximately 15–20% of patients with PLCH experience a pneumothorax. Nearly 63% of those patients will have more than one pneumothorax. Simultaneous bilateral pneumothorax can occur and may be fatal. Due to high rate of recurrence, pleurodesis should be performed following the initial episode of pneumothorax. A study found a recurrence rate of 58% when managed conservatively, compared with 0% following surgical pleurodesis. Treatment of PLCH must involve smoking cessation. The effect of steroids or chemotherapeutics on disease course, and occurrence of pneumothorax, is unclear.
Air travel and diving may lead to cyst expansion and predispose patients with DCLDs to a higher risk of pneumothorax. The risk of pneumothorax associated with air travel has been studied in LAM and, more recently, BHD as discussed in a previous blog. The risk of flight-related pneumothorax is currently being evaluated for patients with PLCH. Studies have concluded that it is safe for most patients with DCLDs to undertake air travel but patients should be educated about the signs and symptoms of a pneumothorax and counselled prior to boarding an airplane. Limited data are available regarding the safety of diving in patients with DCLDs but the authors recommend that patients with DCLDs avoid diving in accordance with the British Thoracic Society guidelines.
Recent data suggest that BHD, LAM, and PLCH likely cause approximately 10% of apparent primary spontaneous pneumothoraces. Current guidelines do not recommend screening CT for first-time pneumothoraces. However, in a recent study, performing a screening HRCT to facilitate early diagnosis of LAM, BHD, or PLCH followed by pleurodesis was found to be cost-effective. Based on this, the authors recommend that all patients with an apparent primary spontaneous pneumothorax be screened with HRCT for the presence of underlying DCLDs.
In summary, DCLDs are being recognized as the cause of spontaneous pneumothoraces. The impact of pneumothoraces on these diseases, the efficacy of alternative techniques to reduce recurrence risk, the impact of targeted pharmacologic therapy on pneumothoraces and the molecular pathways behind them, are some of the major unanswered questions to be addressed.