Spontaneous pneumothorax

Spontaneous pneumothorax in most patients occurs from the rupture of blebs and bullae. Although primary spontaneous pneumothorax (PSP) is defined as occurring in patients without underlying pulmonary disease, these patients have asymptomatic blebs and bullae detected on computed tomography scans or during thoracotomy. PSP is typically observed in tall, young people without parenchymal lung disease and is thought to be related to increased shear forces in the apex. Although PSP is associated with the presence of apical pleural blebs, the exact anatomic site of air leakage is often uncertain. Fluorescein-enhanced autofluorescence thoracoscopy (FEAT) is a novel method to examine the site of air leak in PSP. FEAT-positive lesions can be detected that appear normal when viewed under normal white-light thoracoscopy.[2] In normal respiration, the pleural space has a negative pressure. As the chest wall expands outward, the surface tension between the parietal and visceral pleura expands the lung outward. The lung tissue intrinsically has an elastic recoil, tending to collapse inwards. If the pleural space is invaded by gas from a ruptured bleb, the lung collapses until equilibrium is achieved or the rupture is sealed. As the pneumothorax enlarges, the lung becomes smaller. The main physiologic consequence of this process is a decrease in vital capacity and partial pressure of oxygen. Lung inflammation and oxidative stress are hypothesized to be important to the pathogenesis of PSP.[3] Current smokers, at increased risk for PSP, have increased numbers of inflammatory cells in the small airways. Bronchoalveolar lavage (BAL) studies in patients with PSP reveal that the degree of inflammation correlates with the extent of emphysematouslike changes (ELCs). One hypothesis is that ELCs result from degradation of lung tissue due to imbalances of enzymes and antioxidants released by innate immune cells.[4] In one study, erythrocyte superoxide dismutase activity was significantly lower and plasma malondialdehyde levels higher in patients with PSP than in normal control subjects.[3] A growing body of evidence suggests that genetic factors may be important in the pathogenesis of many cases of PSP. Familial clustering of this condition has been reported. Genetic disorders that have been linked to PSP include Marfan syndrome, homocystinuria, and Birt-Hogg-Dube (BHD) syndrome. Birt-Hogg-Dube syndrome is an autosomal dominant disorder that is characterized by benign skin tumors (hair follicle hamartomas), renal and colon cancer, and spontaneous pneumothorax. Spontaneous pneumothorax occurs in about 22% of patients with this syndrome. The gene responsible for this syndrome is a tumor suppressor gene located on band 17p11.2. The gene encoding folliculin (FLCN) is thought to be the etiology of Birt-Hogg-Dube syndrome. Multiple mutations have been found, and phenotypic variation is recognized. In one study, 8 patients without skin or renal involvement had lung cysts and spontaneous pneumothorax.[5] A germ-line mutation to this gene has been found in 5 patients, and genetic testing is now available.

Tension pneumothorax

Tension pneumothorax occurs anytime a disruption involves the visceral pleura, parietal pleura, or the tracheobronchial tree. This condition develops when injured tissue forms a 1-way valve, allowing air inflow with inhalation into the pleural space and prohibiting air outflow. The volume of this nonabsorbable intrapleural air increases with each inspiration because of the 1way valve effect. As a result, pressure rises within the affected hemithorax. In addition to this mechanism, the positive pressure used with mechanical ventilation therapy can cause air trapping. As the pressure increases, the ipsilateral lung collapses and causes hypoxia. Further pressure increases cause the mediastinum to shift toward the contralateral side and impinge on and compress both the contralateral lung and impair the venous return to the right atrium. Hypoxia results as the collapsed lung on the affected side and the compressed lung on the contralateral side compromise effective gas exchange. This hypoxia and decreased venous return caused by compression of the relatively thin walls of the atria impair cardiac function. Kinking of the inferior vena cava is thought to be the initial event restricting blood to the heart. It is most evident in trauma patients who are hypovolemic with reduced venous blood return to the heart. Arising from numerous causes, this condition rapidly progresses to respiratory insufficiency, cardiovascular collapse, and, ultimately, death if unrecognized and untreated.

Pneumomediastinum
With pneumomediastinum, excessive intra-alveolar pressures lead to rupture of alveoli bordering the mediastinum. Air escapes into the surrounding connective tissue and dissects further into the mediastinum. Esophageal trauma or elevated airway pressures may also allow air to dissect into the mediastinum. Air may then travel superiorly into the visceral, retropharyngeal, and subcutaneous spaces of the neck. From the neck, the subcutaneous compartment is continuous throughout the body; thus, air can diffuse widely. Mediastinal air can also pass inferiorly into the retroperitoneum and other extraperitoneal compartments. If the mediastinal pressure rises abruptly or if decompression is not sufficient, the mediastinal parietal pleura may rupture and cause a pneumothorax (in 10-18% of patients). A wide variety of disease states and circumstances may result in a pneumothorax.

Primary and secondary spontaneous pneumothorax

Risks factors for primary spontaneous pneumothorax (PSP) include the following:

Smoking Tall, thin stature in a healthy person Marfan syndrome Pregnancy Familial pneumothorax

Blebs and bullae (sometimes called emphysematouslike changes or ELCs) are related to the occurrence of primary spontaneous pneumothorax. Thoracic computerized tomography (CT)

scans of patients with PSP shows ipsilateral ELC in 89% and contralateral changes in 80% compared with a rate of 20% among control subjects matched for age and smoking.[1] Nonsmokers with PSP had CT scan ELC abnormalities of 80% compared with a rate of 0% among nonsmoker controls without PSP.[1] Although patients with PSP do not have overt parenchymal disease, this condition is heavily associated with smoking80-90% of primary spontaneous pneumothorax (PSP) cases occur in smokers or former smokers, and the relative risk of PSP increases as the number of cigarettes smoked per day increases; that is, the risk of PSP is related to the intensity of smoking, with 102times higher incidence rates in males who smoke heavily (ie, >22 cigarettes/d), compared with a 7-fold increase in males who smoke lightly (1-12 cigarettes/d). This incremental risk with increasing number of cigarettes smoked per day is much more pronounced in female smokers. Typical PSP patients also tend to have a tall and thin body habitus. Whether height affects development of subpleural blebs or whether more negative apical pleural pressures cause preexisting blebs to rupture is unclear. Pregnancy is an unrecognized risk factor, as suggested by a 10-year retrospective series in which 5 of 250 spontaneous pneumothorax cases were in pregnant women.[6] The cases were all managed successfully with simple aspiration or vacuum-assisted thoracostomy (VATS), and no harm occurred to mother or fetus.[6] Other associations with pneumothorax include increased intrathoracic pressure with Valsalva, although results contrary to popular belief, most spontaneous pneumothoraces occur while the patient is at rest. Changes in atmospheric pressure, proximity to loud music, and low frequency noises are other reported factors. Familial associations have been noted in more than 10% of patients. Some are due to rare connective tissue diseases, but mutations in the gene encoding folliculin (FLCN) have been described. These patients may represent an incomplete penetrance of an autosomal dominant genetic disorder. Birt-Hogg-Dube syndrome is characterized by benign skin growths, pulmonary cysts, and renal cancers and is caused by mutations in the FLCN gene. In one family study, 9 ascertained cases of spontaneous pneumothorax were reported among 54 members. A review of the literature summarized 61 reports of familial spontaneous pneumothorax among 22 families. Up to 10% patients with spontaneous pneumothorax report a positive family history.[7] Although rare, spontaneous pneumothorax occurring bilaterally and progressing to tension pneumothorax has been documented. Diseases and conditions associated with secondary spontaneous pneumothorax include the following:

Chronic obstructive lung disease (COPD) or emphysema: Increased pulmonary pressure due to coughing with a bronchial plug of mucus or phlegm bronchial plug may play a role. Asthma

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) with PCP infection Necrotizing pneumonia Tuberculosis Sarcoidosis Cystic fibrosis Bronchogenic carcinoma or metastatic malignancy Idiopathic pulmonary fibrosis Inhalational and intravenous drug use (eg, marijuana, cocaine)[8] Interstitial lung diseases associated with connective tissue diseases Lymphangioleiomyomatosis Langerhans cell histiocytosis Severe acute respiratory syndrome (SARS): A reported 1.7% of SARS patients developed spontaneous pneumothorax.[9] Thoracic endometriosis and catamenial pneumothorax Collagen vascular disease, including Marfan syndrome

Secondary spontaneous pneumothoraces (SSP) occur in the presence of lung disease, primarily in the presence of COPD. Other diseases that may be present when SSPs occur include tuberculosis, sarcoidosis, cystic fibrosis, malignancy, and idiopathic pulmonary fibrosis. Pneumocystis jiroveci pneumonia (previously known as Pneumocystis carinii pneumonia [PCP]) was a common cause of SSP in patients with AIDS during the last decade. In fact, 77% of AIDS patients with spontaneous pneumothorax had thin-walled cavities, cysts, and pneumothorax from PCP infection.[10] With the advent of highly active antiretroviral therapy (HAART) and widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis, the incidence of PCP and associated SSP has significantly declined. PCP in other immunocompromised patients is seen only when TMP-SMZ prophylaxis is withdrawn prematurely. For practical purposes, if the immunocompromised patient has been taking TMP-SMZ prophylaxis reliably, PCP is reasonably excluded from the differential diagnosis and should not be a causative factor for SSP. In cystic fibrosis, up to 18.9% of patients have been reported to develop spontaneous pneumothoraces, and they have a high incidence of recurrence on the same side after conservative management (50%) or intercostal drainage (55.2%). The risk of SSP in these patients increases with Burkholderia cepacia or Pseudomonas infections and allergic bronchopulmonary aspergillosis (ABPA).[11] Pleurodesis increases the risk of bleeding associated with lung transplantation but is not an absolute contraindication. Many different types of malignancies are known to present with a pneumothorax, especially sarcomas, but also genitourinary cancers and primary lung cancer; thus, pneumothorax in a patient with malignancy should prompt a look for metastatic disease. Chemotherapeutic agents, at times, can also induce SSP.[12]

Interstitial lung diseases are associated with connective-tissue diseases. Ankylosing spondylitis may be noted when apical fibrosis is present; in fact, the typically low incidence of spontaneous pneumothorax in patients with ankylosing spondylitis (0.29%) increases 45-fold (to 13%) when apical fibrotic disease exists.[13] Lymphangioleiomyomatosis (LAM) may present with spontaneous pneumothorax. This disease is characterized by thin-walled cysts in women of childbearing age. Respiratory failure may lead to a need for lung transplantation, and previous pleurodesis is no longer an absolute contraindication for lung transplantation. Thoracic endometriosis is a rare cause of recurrent pneumothorax (catamenial pneumothorax) in women that is thought to arise from endometriosis reaching the chest wall across the diaphragm (ie, its etiology may be primarily related to associated diaphragmatic defects). In a case series of 229 patients, catamenial pneumothorax caused by thoracic endometriosis was localized to the visceral pleura in 52% of patients and to the diaphragm in 39% of patients.[14] Before recurrence, this condition may be initially diagnosed as primary spontaneous pneumothorax.

Iatrogenic and traumatic pneumothorax

Causes of iatrogenic pneumothorax include the following:

Transthoracic needle aspiration biopsy of pulmonary nodules (most common cause, accounting for 32-37% of cases) Transbronchial or pleural biopsy Thoracentesis Central venous catheter insertion, usually subclavian or internal jugular[15] Intercostal nerve block Tracheostomy Cardiopulmonary resuscitation (CPR): Consider the possibility of a pneumothorax if ventilation becomes progressively more difficult. Acute respiratory distress syndrome (ARDS) and positive pressure ventilation in the ICU: High peak airway pressures can translate into barotrauma in up to 3% of patients on a ventilator and up to 5% of patients with ARDS.[16] Nasogastric feeding tube placement

Iatrogenic pneumothorax is a complication of medical or surgical procedures. It most commonly results from transthoracic needle aspiration. Other procedures commonly causing iatrogenic pneumothorax are therapeutic thoracentesis, pleural biopsy, central venous catheter insertion, transbronchial biopsy, positive pressure mechanical ventilation, and inadvertent intubation of the right mainstem bronchus. Therapeutic thoracentesis is complicated by pneumothorax 30% of the time when performed by inexperienced operators in contrast to only 4% of the time when performed by experienced clinicians. The routine use of ultrasonography during diagnostic thoracentesis is associated with lower rates of pneumothorax (4.9% vs 10.3%) and need for tube thoracostomy (0.7% vs 4.1%). Similarly, in

patients who are mechanically ventilated, thoracentesis guided by bedside ultrasonography without radiology support results in a relatively lower rate of pneumothorax. Causes of traumatic pneumothorax include the following:

Trauma: Penetrating and nonpenetrating injury Rib fracture High-risk occupation (eg, diving, flying)

Traumatic pneumothoraces can result from both penetrating and nonpenetrating lung injuries. Complications include hemopneumothorax and bronchopleural fistula. Traumatic pneumothoraces often can create a 1-way valve in the pleural space (only letting in air without escape) and can lead to a tension pneumothorax.

Tension pneumothorax
The most common etiologies of tension pneumothorax are either iatrogenic or related to trauma, such as the following:

Blunt or penetrating trauma: Disruption of either the visceral or parietal pleura occurs and is often associated with rib fractures, although rib fractures are not necessary for tension pneumothorax to occur. Barotrauma secondary to positive-pressure ventilation, especially when using high amounts of positive end-expiratory pressure (PEEP) Pneumoperitoneum[17, 18] Fiberoptic bronchoscopy with closed-lung biopsy[19] Markedly displaced thoracic spine fractures Acupuncture[20, 21, 22] Preexisting Bochdalek hernia with trauma[23] Colonoscopy[24] and gastroscopy have been implicated in case reports. Percutaneous tracheostomy[25] Conversion of idiopathic, spontaneous, simple pneumothorax to tension pneumothorax Unsuccessful attempts to convert an open pneumothorax to a simple pneumothorax in which the occlusive dressing functions as a 1-way valve

Tension pneumothorax occurs commonly in the ICU setting in patients who are ventilated with positive pressure, and practitioners must always consider this when changes in respiratory or hemodynamic status occur. Infants requiring ventilatory assistance and those with meconium aspiration have a particularly high risk for tension pneumothorax. Aspirated meconium may serve as a 1-way valve and produce a tension pneumothorax. Any penetrating wound that produces an abnormal passageway for gas exchange into the pleural spaces and that results in air trapping may produce a tension pneumothorax. Blunt trauma, with or without associated rib fractures, and incidents such as unrestrained head-on motor vehicle accidents, falls, and altercations involving laterally directed blows may also cause tension pneumothoraces.

Significant chest injuries carry an estimated 10-50% risk of associated pneumothorax; in about 50% of these cases, the pneumothorax may not be seen on standard radiographs and are therefore deemed occult. In one study, 12% of patients with asymptomatic chest stab wounds had a delayed pneumothorax or hemothorax. McPherson et al analyzed data from the Vietnam Wound Data and Munitions Effectiveness Team study and determined that tension pneumothorax was the cause of death in 3-4% of fatally wounded combat casualties.[26] Acupuncture is a traditional Chinese medicine technique used worldwide by alternative medical practitioners. Acupuncture's most frequently reported serious complication is pneumothorax; in one Japanese report of 55,291 acupuncture treatments, an approximate incidence of 1 pneumothorax in 5000 cases was documented.[27]

Pneumomediastinum
The following factors may result in pneumomediastinum:

Acute generation of high intrathoracic pressures (often as a result of inhalational drug use, such smoking marijuana or inhalation of cocaine) Asthma Respiratory tract infection Parturition Emesis Severe cough Mechanical ventilation Trauma or surgical disruption of the oropharyngeal, esophageal, or respiratory mucosa Athletic competition