Secondary Pneumothorax from a Surgical Perspective

Abstract

Although less frequent than the primary spontaneous pneumothorax (PSP), secondary pneumothoraces (SP) are a common clinical problem with a wide range of severity, depending on the triggering cause(s) and patient clinical condition. By definition, an SP occurs in those patients with an underlying condition that alters the normal lung parenchyma and/or the visceral pleura and determines air entry in the pleural space (e.g., COPD) or, eventually, following trauma or invasive procedures (i.e., iatrogenic pneumothorax). Less frequent, yet described, is SP occurring in neoplastic patients or infectious ones. The gravity of an SP is directly correlated to the underlying cause and patients’ clinical conditions. For example, it may be a life-threatening condition in an end-stage COPD but less severe in a catamenial related syndrome. In this chapter, we are providing a surgical overview of the most relevant and updated information on etiology, incidence, pathophysiology, and management of secondary pneumothoraces.

1. Introduction

Pneumothorax (PNX) is an abnormal collection of air in the pleural space. It is defined as primary spontaneous pneumothorax (PSP) or secondary, based on age, causes, and the requirement of different management [1].

A PSP usually occurs following the rupture of subvisceral pleural blebs and its cause is unknown. Most frequently, patients are males, healthy teenagers or young adults, and smokers [2].

Instead, a spontaneous secondary pneumothorax (SPS) is often associated with a known lung disease and the main cause is a chronic obstructive pulmonary disease (COPD). Other causes are, for instance, idiopathic fibrosis, acquired immunodeficiency syndrome (AIDS), and neoplastic disease. Secondary pneumothorax (SP) could also occur after a chest trauma (post-traumatic pneumothorax) or after invasive procedures (iatrogenic). A specific subgroup is represented by the catamenial pneumothorax, as discussed further on.

The annual incidence of SPS is in general 26 cases per 100.000 and it is more common in men with a 3:1 ratio. It is mainly observed in patients aged 50–60 years old [3, 4].

In general, symptoms include chest pain and shortness of breath, but symptoms could differ according to the cause of pneumothorax [5].

In the following chapter, all the aspects related to a secondary pneumothorax are described.

2. Secondary pneumothorax

The annual incidence of an SP is approximately 6.3 cases per 100.000 in men and 2 cases per 100.000 in women, every year [3].

A SP may occur:

• in the presence of pre-existing lung diseases, like COPD, infections (e.g., tuberculosis, necrotizing pneumonia, and pneumocystis carinii), inflammatory disease (e.g., rheumatoid arthritis, polymyositis and dermatomyositis, and systemic sclerosis);

• in the presence of neoplastic disease (e.g., primary lung cancer, sarcoma metastases, and malignant pleural mesothelioma);

• as a consequence of a chest trauma;

• as a complication of medical or surgical procedures (iatrogenic pneumothorax); or

• concomitant to other pre-existing pathologies (e.g., catamenial pneumothorax) [6].

Moreover, compared to a primary pneumothorax, SP afflicts patients with a known history of lung disease. For such reasons, an SP:

• is less tolerated by patients because of a co-existing lung disease;

• is generally characterized by the presence of a persistent air leak that does not tend to resolve spontaneously, requiring an active intervention; and

• oxygen could be required to promote air reabsorption, especially in the case of subcutaneous emphysema.

Generally, the management of such patients is complex and the treatment requires a chest tube insertion, prolonged hospitalization, and consideration for a surgical procedure to induce pleurodesis.

2.1 Secondary pneumothorax in nonneoplastic lung disease

2.1.1 Definition and incidence

The main cause of SP is COPD, with an incidence of 26 cases per 100.000 patients per year [7]; COPD is one of the three main causes of death in the world and one of the main causes of chronic disease [8].

Based on computed tomography (CT) images, COPD may be divided into:

• emphysema- and airway-dominant COPD: SP generally occurs as a consequence of bullae disruptions (Figure 1);

• nonemphysematous COPD.

Figure 1.

Emphysema dominant COPD.

According to the GOLD guideline [9], COPD severity depends on pulmonary function, evaluated by means of a spirometry. The risk of an SP is higher in patients affected by severe COPD. Patients with FEV1 < 1 L and/or a FEV1/FVC < 40% are deemed at high-risk [10], with a common observance of severe hypoxemia associated with hypercapnia in case of pneumothorax [8].

The development of a secondary pneumothorax in COPD patients is a parameter of high mortality and, in fact, it has been demonstrated that each SP event increases fourfold the chances of death in such patients [11].

2.1.2 Pathophysiology and clinical features

When a pneumothorax occurs in a COPD patient with a low respiratory function, it is common to observe severe hypoxemia caused by a lower ventilation-perfusion (V/Q) rate, which is capable to determine an incremented shunt that is directly proportional to the PNX size. Compensatory hypercapnia is often associated [8].

For such reasons, an SP onset in COPD patients is generally associated with a rapidly progressive dyspnea and pleuritic chest pain where a prompt management is mandatory.

2.1.3 Diagnosis

Generally, COPD patients present with hyperinflated lungs and abnormal lung auscultation. A reduced or absent vesicular murmur associated with symptoms such as shortness of breath, low saturation, and hyperventilation should easily guide to diagnose a PNX.

A chest X-ray is mandatory to assess the presence of a PNX, which usually appears as a complete collapse of the lung. Seldomly, a subcutaneous emphysema may occur, concealing the PNX at the chest X-ray (Figure 2).

Figure 2.

Massive subcutaneous emphysema. Red arrow to indicate the small size SP.

Generally, at chest X-ray, bullous lesions have a concave appearance while a pneumothorax has a concave profile (Figure 3).

Figure 3.

The different appearance between an SP and bullae. Image a: a secondary pneumothorax in a COPD patient. At the chest X-ray, a pneumothorax has a concave profile. Image b: bulls lesion has a concave appearance.

In COPD patients, however, a CT scan is useful to better analyze the pneumothorax size and the severity of the lung disease. Moreover, The CT scan can help in distinguishing a big bulla from a true PNX. This may not be an easy task; however, if a bulla is detected, a chest tube is not always indicated, or if it is, it should be carefully placed under CT guidance, in order to avoid an iatrogenic rupture of the bulla determining a complex PNX, which potentially requires a surgical treatment.

It is important to remember that due to the underlying pathology and the low functional reserve, these patients could become suddenly critical in case of a PNX and should therefore be treated accordingly. For the same reason, even if the PNX is correctly treated by means of a chest drain, these patients still remain at a higher risk of death. Death causes are, in fact, associated with the onset of an acute or late respiratory failure [12, 13], or with a higher risk of developing sepsis as a consequence of pneumonia or empyema due to the pneumothorax management (i.e., chest tube and/or pleurodesis) [14].

2.1.4 Other causes of SP in non-COPD patients

Any noxa capable to affect the integrity of the visceral pleura and reduce the lung elasticity could be a cause of a secondary pneumothorax and therefore, a secondary pneumothorax may be diagnosed in the process of:

1. Infection: tuberculosis, necrotizing pneumonia, and Pneumocystis carinii (it determines an infection capable of recalling macrophages in the lung parenchyma with consequent tissue destruction and fibrosis), viral or mycotic infection (Figure 4). In these cases, a medical treatment is mandatory before considering surgery as an option to resolve the SP.

2. Interstitial diseases: cystic fibrosis, acute severe asthma. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrosing lung disease of unknown etiology. The rates of pneumothorax range from 2 to 20% in patients with IPF, becoming the second cause of SP after chronic obstructive pulmonary disease (COPD) [15].

3. Inflammatory or connective-related diseases: such as rheumatoid arthritis, polymyositis, dermatomyositis, systemic sclerosis, Marfan’s syndrome, and Ehlers-Danlos syndrome.

Figure 4.

Pneumothorax caused by tubercular infection.

Acquired immunodeficiency syndrome (AIDS) could be another cause of SP, likely related to an increased risk of developing cystic lesions in the sub-pleural space [16].

2.1.5 Management

As in the case of primary pneumothorax, the treatment goals should aim at:

• evacuating the pleural cavity from the air to restore the normal intrapleural negative pressure;

• obtaining lung re-expansion and pleural apposition;

• reducing the risk of recurrence.

According to the BTS guidelines, a secondary pneumothorax that occurred in a known diseased lung requires the insertion of a small-bore chest tube to drain the air in the pleural space [17].

Pneumothorax aspiration, which finds a treatment indication in the primary spontaneous pneumothorax, has a high-risk of failure, but it may be taken into account in the case of symptomatic patients with a small pneumothorax. A persistent air leak can be managed conservatively obtaining a complete resolution [17].

A talc slurry pleurodesis could be a nonsurgical therapeutic management option to be considered for persistent air leak in patients deemed unfit for surgery. According to the American College of Chest Physicians (ACCP) consensus, a talc slurry pleurodesis through the chest tube is indicated to avoid recurrence after the first episode [14].

By contrast, the BTS guidelines suggest pleurodesis in case of a recurrent SP or in case of a persistent air leak, which in COPD patients may resolve in a long time compared to non-COPD patients [18]. Surgery is an option in SP, but COPD patients may not be deemed fit enough for surgery because of their clinical status. A prerequisite for talc pleurodesis is a complete or major re-expansion of the lung. In case of partially expanded or nonexpandable lungs, other options should be advocated, such as permanent drains connected to a Heimlich valve. Furthermore, prior to proceeding to talc pleurodesis, the increased risk of a pulmonary restrictive dysfunction secondary to talc insufflation should be well pondered and discussed interdisciplinary.

Contrarily to the ACCP guidelines that suggest medical thoracoscopy or VATS as the first choice to perform talc pleurodesis, because of their lower morbidity, the BTS guidelines consider an open approach (thoracotomy) as the procedure of choice, limiting VATS procedures to unfit patients [17].

Furthermore, in nonsurgical patients with a persistent air leak a talc slurry via chest tube should be taken into consideration.

2.1.5.1 Focus on: management of emphysema-dominant COPD lung volume reduction surgery (LVRS)

The 2021 GOLD guidelines consider as the main surgical option in high-grade COPD [9]:

• lung volume reduction surgery (LVRS);

• bullectomy/blebectomy, which are associated with an improvement of dyspnea and lung function;

• lung transplantation: in very high-risk patients, with progressive COPD. Inclusion criteria are exacerbations associated with hypercapnia (pCO2 ≥ 50 mmHg), pulmonary hypertension, FEV1 < 20%, and/or a diffusing capacity for carbon monoxide (Dlco <20%) [9].

LVRS can improve survival in severe lung emphysema, mainly in the upper lobes localized emphysema, and low-ability exercise patients [17]. The National Emphysema Treatment Trial (NETT) identified four groups of patients [19] on the basis of their postoperative exercise tolerance and their emphysema pattern at the CT scan (Table 1).

Emphysema at CT scan	Pre-operative exercise capacity	LVRS risk of death	Survival	Post-operative exercise tolerance	Symptoms control
Upper lobe-predominant emphysema	Low	Lower than medical therapy	Improved	Improved within 3 years from surgery	Improved
	High		Not improved	Improved (years 1–3)	Improved (years 1–4)
Non-upper lobe-predominant emphysema	Low	No effects	Not improved	No effects
	High	Increased	Not improved	No effects	No effects

Table 1.

Results in the four groups studied in the NETT trial.

The NETT demonstrated that the effects of LVRS are durable and that it is strongly recommended in upper lobe-predominant emphysema with low exercise capacity and should be considered for palliation in patients with upper lobe emphysema and high exercise capacity (Figure 5).

Figure 5.

Results of NETT. Image D: Upper lobe–predominant emphysema with low exercise capacity group. The surgical group has a lower probability of death than the medical group.

2.1.5.2 Endobronchial valves

Predominantly, the following endobronchial procedures find an indication in reducing the end-expiratory lung volume and to improve exercise tolerance:

• endobronchial lung volume reduction with one-way valves (BLVR);

• endobronchial coils filling;

• thermal ablation.

Endobronchial valves are placed in segmental or lobar bronchi through rigid bronchoscopy, allowing peripheral lung deflation, lung volume reduction, and improvement of symptoms with an accepted mortality rate equal to 5–10% [20]. The valve mechanism does not permit air to go through the segmental or lobar bronchus during the inspiration but, instead, it allows it passage during the expiratory phase. The valves are available in multiple diameters, ranging from 4 to 8.5 mm.

In general, two main devices are available:

• the “aspiration umbrella”, which is an implantable Intra-Bronchial Valve (IBV) that can be positioned via flexible bronchoscopy, leaving the umbrella shape adherent to the airway wall and limiting the airflow distally;

• the Emphasis Bronchial Valve (EBV), which is able to prevent air entering in the lung during inspiration but allows outflow of air and secretion. A flexible aspiration valve is present in the endobronchial valve structure from which exhaled air and secretions can be cleared out or aspirated because of the unidirectional valve.

Both devices are inserted in the operating theater with the patient sedated and in spontaneous assisted (jet-) ventilation [21].

The VENT trial (Endobronchial Valve for Emphysema Palliation Trial) [22] is a two-arm, randomized, controlled, multi-center trial that showed a 4.3% FEV1 increase in the EBV group compared to the 2.5% in the control medical group.

However, the study shows that complications following the procedure may counterbalance the advantages of the procedure itself. In fact, on the one hand, patients may obtain an improvement in their respiratory function, and on the other hand, it may be associated with hemoptysis, pneumothorax with persistent air leak, and COPD exacerbations, which may occur more frequently in advanced, hyper-inflated emphysema patients. Moreover, as evidenced in the VENT trial, the 2-yrs mortality rate in the EBV group was 2.8% compared to no deaths in the control group, but the difference wasn’t statistically significant (p = 0.19).

2.2 Secondary pneumothorax in concomitant neoplastic disease

Although rare findings, the main causes of SP from malignant diseases are primary cancers of the lung and pleura (e.g., mesothelioma) followed by infiltrative/metastatic pleural diseases, such as in the case of germ cell tumors, breast cancer, or osteogenic and soft tissue sarcomas metastasis [21, 22, 23].

2.2.1 Incidence

The occurrence of an SP as the first manifestation of a lung cancer ranges between 0.03% and 0.05% and usually allows to detect the unknown presence of a lung tumor or metastasis [24] without affecting the prognosis [25, 26].

By contrast, a review published in 2010 analyzed data available in the literature concerning pneumothorax secondary to sarcoma, highlighting increased mortality in such patients compared to those without such complications [26].

2.2.2 Pathophysiology

Several hypotheses have been taken into account to explain the pathogenesis of pneumothorax secondary to malignant disease, which include (i) an alteration of the pleural surface following tumoral pleural infiltration; (ii) rupture of a necrotic tumoral nodule; and (iii) necrosis of subpleural metastases [27].

Moreover, adjuvant or neoadjuvant chemotherapy and/or radiotherapy treatments may alter the lung parenchymal structure. In these cases, the high-risk of infection associated with a reduced functional repair mechanism could enhance the risk of pleural alterations, possibly leading to a secondary pneumothorax. Also, a tumoral invasion of the small airways could be responsible for a distal alveolar space dilatation determining air-trapping, which may lead to rupture and pneumothorax.

2.2.3 Clinical features and diagnosis

The clinical presentation depends on the patients’ performance status according to their functional status and disease stage. Usually, clinical signs and symptoms are chest pain and shortness of breath.

A chest X-ray is mandatory to assess the presence of a pneumothorax, which usually appears as a complete collapse of the normal areas of the lung. A CT scan is useful to better analyze the pneumothorax size and to investigate a possible progression of disease.

Pneumothorax can be the first sign of neoplastic disease, especially when it assumes a recurrent nature in high-risk patients (heavy smokers, COPD), who will therefore undergo further investigations, which will lead to eventually diagnose the tumor.

2.2.4 Management

Diagnosis and management of a secondary pneumothorax concomitant to a pulmonary neoplastic disease are the same for a pneumothorax happening in a pre-existing neoplastic condition. A chest tube is recommended according to its size and the clinical features of patients.

In case of a persistent air leak or in a recurrent pneumothorax, surgery is an option in order to investigate the causes and proceed to talc pleurodesis in case of nonoperable tumors or unfit for surgery patients. If surgery is contemplated, the surgeon may proceed to obtain a diagnosis in case this was not achieved previously, by means of pleural biopsy/wedge resection/lymph node sampling. Cases of recurrent pneumothorax as the first sign of pleural mesothelioma or sarcoma metastasis have been reported, identifying the thoracoscopic bullectomy as the key to the best diagnosis and treatment [28, 29].

2.3 Secondary pneumothorax in chest trauma

2.3.1 Incidence

Thoracic trauma is the third leading cause of death following abdominal injury and head trauma in polytrauma patients [30]. Management of chest trauma patients is complex and requires an interdisciplinary team with experience in anesthesia, critical care, and surgical disciplines, especially neurosurgery, trauma surgery, abdominal surgery, and thoracic surgery.

Blunt and penetrating chest traumas can be the cause of pneumothorax and trauma should be taken into account when discussing secondary pneumothoraces.

2.3.2 Definition

Thoracic trauma can be differentiated into blunt or penetrating.

Penetrating injuries, such as blade wounds and firearm injuries, are disruptive to tissue integrity. Gunshot and stabbing account for 10% and 9.5% of penetrating chest injuries, making these the most common etiology of penetrating trauma.

A blunt trauma (Figure 6) is a nonpenetrating injury of the chest. Blunt thoracic injuries are more common than penetrating injuries [30].

Figure 6.

Pneumothorax after a barotrauma.

Blunt injuries can cause damage to organs and structures without disrupting the integrity of the tissue. Falls from a great height, motor vehicle accidents, and occupational accidents are the main mechanisms of blunt injuries [31, 32, 33].

2.3.3 Diagnosis

Depending on the mechanism of injury (e.g., acceleration-deceleration and direct impacts on the chest) an SP may be detected and should be treated and investigated on the cause of its onset (rib fractures, tracheal/bronchial or esophageal disruptions, lung contusion, and lung laceration).

Particular attention is reserved for a tension pneumothorax, in which air enters the pleural space at each inspiration, while the air in the pleural space cannot escape from the pleural space due to the one-way valve mechanism. The continuous accumulation of air in the pleural space determines a lung collapse, hypoxia, tachypnea, and tachycardia, a mediastinal shift with compression of the contralateral lung and the superior vena cava (SVC), leading to respiratory distress and rapidly to respiratory failure with cardiovascular collapse.

2.3.4 Management

Management of patients following major trauma should follow the standardized protocol of emergency and resuscitation advanced trauma life support guidelines (ATLS), and a primary survey of the airway, breathing, circulation, disability, and exposure (ABCDE approach) should be performed.

Particular attention is required in a tension pneumothorax because, if a prompt intervention is not carried out, can rapidly lead to death [34]. Immediate evacuation through a chest tube is mandatory as recommended by the ATLS [35].

In general, a chest tube has to be positioned in a post-traumatic pneumothorax, in order to stabilize the patient.

Once the patient is stabilized, radiological investigations, such as chest X-ray and chest CT scan are mandatory to identify the cause of pneumothorax and eventually determine the need for further treatments (surgery).

At the same time, minor blunt traumas may be cause of small pneumothoraces, which may not require a chest tube and can be treated conservatively with high flow oxygen, pain control, and repeated CXR [36].

Penetrating injuries are disruptive to tissue integrity, with direct communication between the pleural space and the external environment and they can be acutely life-threatening.

It is mandatory to know the mechanism of injury as the management may vary. For example, stab versus gunshot injury to the chest can result in different patterns of injury.

Depending on the penetrating trauma, immediate surgery may be deemed necessary and a chest tube is required to stabilize the patient for surgery (e.g., during patient transportation from the trauma site to the hospital). Frequently, when a post-traumatic pneumothorax is present it can be associated with a hemothorax [37].

2.4 Secondary pneumothorax after invasive procedures (iatrogenic pneumothorax)

Iatrogenic pneumothorax is a possible complication of several invasive procedures, such as a central venous line insertion (0.5–5%), thoracentesis (1, 5–7%), and CT-guided lung biopsy (1–6%); at times they can be associated with hemothorax (1% of all procedures) [38, 39].

In some cases, it may occur as a complication following bronchoscopic positioning of unidirectional valves in emphysematous patients [21].

2.5 Catamenial pneumothorax

The term “catamenial” derives from two Greek words meaning “pertaining to” and “monthly.”

Catamenial pneumothorax is defined as a recurrent accumulation of air in the pleural cavity in reproductive-age women.

2.5.1 Incidence and etiology

A catamenial pneumothorax (CP) arises within 48–72 h from menstruation. It occurs in 3–6% of spontaneous pneumothoraces and most frequently involves the right side [40].

This kind of pneumothorax is, mainly, included in two syndromes:

• the thoracic endometriosis syndrome (TES), which is associated with hemothorax and lung nodules. It is a rare clinical disease that sometimes is secondary to the presence of endometrial gland tissue in the lungs, pleura, diaphragm, and tracheobronchial tree [41]. TES has been reported for the first time in 1953, in a case report of a young woman that developed hemothorax. In 1958, Mauerer described recurrent pneumothoraces in association with menstruation and pelvic endometriosis [42].

• the porous diaphragmatic syndrome: cases of CP without any evidence of endometrial implants, but secondary to the presence of diaphragmatic defects [43]. In rare cases, in fact, diaphragm fenestrations over the tendinous portion may be visualized during surgery and appear as orifices in the muscle, becoming the cause of pneumothorax.

2.5.2 Diagnosis

The cancer antigen 125 (CA-125), a gynecological serum marker, has assumed a role in the diagnostic work-up for TES. In fact, high levels of CA-125 have been associated with recurrent SP with evidence of thoracic endometriosis, such as focal thoracic endometrial implants, during VATS procedures. On the contrary, patients without thoracoscopic evidence of endometrial disease have normal CA-125 serum level [44].

The presence of a CP is not always related to pelvic endometriosis.

In a prospective study, 32 women had a CP diagnosis, but only 2 had pelvic endometriosis associated [41].

2.6 Pneumothorax and pregnancy

The occurrence of PSP in women of childbearing age is not unusual and there appears to be an increased risk of recurrence during pregnancy and during parturition with potential risks to the mother and fetus.

A more recent case series and literature review have recommended the use of more modern conservative management methods for which favorable outcomes have now been experienced [17, 45]. Pneumothorax in pregnancy can be managed by simple observation, if the mother is not symptomatic, there is no fetal distress and the pneumothorax is small (<2 cm). Otherwise, aspiration can be performed, chest drain insertion being reserved for those with a persistent air leak or a greater pneumothorax.

To avoid spontaneous delivery or cesarean section, both of which have been associated with an increased risk of recurrence, the safest approach will usually be that of elective assisted delivery at or near term. Less maternal effort is required with forceps delivery, which is therefore preferable. Because of the risk of recurrence in subsequent pregnancies, a minimally invasive VATS surgical procedure should be considered few weeks from delivery. Successful pregnancies and spontaneous deliveries without pneumothorax recurrence have been reported after a VATS procedure [17, 45].

3. Conclusions

In contrast to the benign clinical course of a PSP, SP is associated with pre-existing underlying lung disease, trauma, or invasive procedures and can be a life-threatening event. Patients with pre-existing lung disease tolerate a pneumothorax less well, and the distinction between PSP and SSP should be made at the time of diagnosis to guide appropriate management. The consequences of a pneumothorax in patients with a pre-existing lung disease are significantly greater, and the management is potentially more complex than in PSP patients. Furthermore, SP is correlated to a higher morbidity and mortality compared to PSP. Differently from a PSP, where the management is well defined by different international guidelines, SP treatment may vary because of the clinical conditions, previous episodes, severity and duration of symptoms, and the presence of an underlying pulmonary disease. Its treatment will therefore vary accordingly, from observation to needle aspiration or thoracostomy tube drainage with or without pleurodesis and potentially escalating to an open thoracotomy or VATS procedures, as described in this chapter. In case of surgery in high-risk patients (e.g., COPD patients, frail patients), the risk of proceeding to surgery with the aim of resolving the underlying cause and securing the lung with adequate pleurodesis should be well pondered both from the surgical and anesthesiological point of view based onto the patients’ clinical status and consent.