Spontaneous Pneumothoraces in Patients with Birt-Hogg-Dubé Syndrome

Abstract

Rationale: Spontaneous pneumothorax is a common complication of Birt-Hogg-Dubé syndrome (BHD).

Objectives: The optimal approach to treatment and prevention of BHD-associated spontaneous pneumothorax, and to advising patients with BHD regarding risk of pneumothorax associated with air travel, is not well established.

Methods: Patients with BHD were recruited from the Rare Lung Diseases Clinic Network and the BHD Foundation and surveyed about disease manifestations and air travel experiences.

Results: A total of 104 patients completed the survey. The average age at diagnosis was 47 years, with an average delay from first symptoms of 13 years. Pulmonary cysts were the most frequent phenotypic manifestation of BHD, present in 85% of patients. Spontaneous pneumothorax was the presenting manifestation that led to the diagnosis of BHD in 65% of patients, typically after the second episode (mean, 2.4 episodes). Seventy-nine (76%) of 104 patients had at least one spontaneous pneumothorax during their lifetime, and 82% had multiple pneumothoraces. Among patients with multiple pneumothoraces, 73% had an ipsilateral recurrence, and 48% had a subsequent contralateral spontaneous pneumothorax following a sentinel event. The mean ages at first and second pneumothoraces were 36.5 years (range, 14-63 yr) and 37 years (range, 20-55 yr), respectively. The average number of spontaneous pneumothoraces experienced by patients with a sentinel pneumothorax was 3.6. Pleurodesis was generally performed after the second (mean, 2.4) ipsilateral pneumothorax and reduced the ipsilateral recurrence rate by half. A total of 11 episodes of spontaneous pneumothorax occurred among eight patients either during or within the 24-hour period following air travel, consistent with an air travel-related pneumothorax rate of 8% per patient and 0.12% per flight. Prior pleurodesis reduced the occurrence of a subsequent flight-related pneumothorax.

Conclusions: Spontaneous pneumothorax is an important, recurrent manifestation of pulmonary involvement in patients with BHD, and pleurodesis should be considered following the initial pneumothorax to reduce the risk of recurrent episodes. In general, in patients with BHD, pneumothorax occurs in about 1-2 per 1,000 flights, and the risk is lower among patients with a history of prior pleurodesis.

Keywords: Birt–Hogg–Dubé syndrome; air travel; pleurodesis; pneumothorax.

Figure 1.

Flow diagram depicting the subject recruitment and selection for our study. BHD = Birt–Hogg–Dubé syndrome; RLD-CN = Rare Lung Diseases Clinic Network.

Figure 2.

Histogram depicting age at first and second pneumothorax and age at diagnosis of patients with Birt–Hogg–Dubé syndrome. Most patients developed a first and second pneumothorax between the ages of 21 and 50 years, usually before the diagnosis of Birt–Hogg–Dubé syndrome was established.

Figure 3.

Number of spontaneous pneumothoraces per patient.

Figure 4.

Incidence and recurrence of ipsilateral and contralateral pneumothorax in patients with Birt–Hogg–Dubé syndrome. SP = spontaneous pneumothorax.

Figure 5.

Number of episodes of spontaneous pneumothoraces experienced by patients prior to ipsilateral pleurodesis. SP = spontaneous pneumothorax.

Figure 6.

Effectiveness of treatment of pneumothorax in patients with Birt–Hogg–Dubé syndrome. Each hemithorax was considered separately. The highest recurrence rates of pneumothorax occurred with conservative therapy, but surgical and chemical pleurodesis procedures also frequently failed. After the first recurrence episode, almost all patients experienced another pneumothorax if managed conservatively. *Includes observation, simple aspiration, and tube thoracostomy without pleurodesis. SP = spontaneous pneumothorax.