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Bullous Emphysema

Author: Najam A. Siddiqui Author: Abdulghani Sankari Author: Mohamed K. Mansour Editor: Vinod Nookala Updated: 4/12/2025 1:41:15 AM

Introduction

Emphysema is a form of chronic obstructive pulmonary disease (COPD) marked by airflow limitation due to the irreversible destruction and enlargement of alveolar spaces beyond the terminal bronchioles.[1] This loss of distal lung architecture often leads to bullae formation, an air-filled space larger than 1 cm, resulting from damaged lung parenchyma (see Image. Bilateral Bullous Emphysema, Computed Tomography). Approximately 80% of patients who present with bullae also have emphysema, and though terminology varies, the condition is often called bullous emphysema. Alternative terms like emphysematous bullae, giant emphysematous bullae, and bullous lung diseases are also common.[2] A giant bullae encompasses 30% or more of a hemithorax. The standard classifications of bullous emphysema are as follows:

  • Type I: Isolated bullae without widespread emphysema
  • Type II: Subpleural bullae
  • Type III: Widespread bullae throughout the lung [2]

Emphysema is often sub-classified into groups based on the primary location of the emphysematous disease within the lung and acinus, a cluster of alveoli supplied by a single respiratory bronchiole. An acinus in the lungs is the smallest functional unit of the respiratory system. Proximal acinar or centrilobular emphysema refers to the destruction of the central portion of the acinus, which has general associations with smoking. Panacinar emphysema destroys all parts of the acinus and is usually related to α-1 antitrypsin deficiency.[3] Distal acinar or paraseptal emphysema involves the alveolar ducts and often occurs in combination with the previously listed forms of emphysema.[4] 

Patients with COPD often present with progressive shortness of breath, productive cough, wheezing, and reduced exercise tolerance, though symptoms may develop gradually and remain unnoticed until later stages. Physical exam findings may include signs of lung hyperinflation, diminished breath sounds, wheezing, and signs of right heart strain. Pulmonary function tests are the cornerstone in establishing the diagnosis of emphysema, with chest radiography and laboratory testing such as a complete blood count, serum electrolytes, renal function, and thyroid function studies carried out to exclude other causes of dyspnea. Computed tomography may be necessary in patients with suspected complications, who are due for lung cancer screening, or if healthcare professionals are unable to distinguish bullae from a pneumothorax.

The management of bullous emphysema centers around smoking cessation and optimizing medical management. Patients who continue to have persistent symptoms or have giant bullae encompassing 30% or more of a hemithorax may require surgical intervention. Potential surgical interventions include lung volume reduction surgery, bullectomy, and placement of one-way valves using a bronchoscope, which allows trapped air to escape and reduces lung volumes. 

Etiology

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Etiology

The 2 most common causes of emphysema are smoking and α-1 antitrypsin deficiency, an inherited autosomal codominant genetic condition affecting the lungs, liver, and sometimes the skin.[5][6] Most commonly, smoking and COPD cause bullae formation, though some cases are idiopathic.[7]

Additionally, less common causes of emphysema and bullae unrelated to tobacco use include the following: 

  • Intravenous substance abuse leading to inflammatory or destructive damage to the alveoli
  • Electronic cigarettes
  • Smoking marijuana or crack cocaine
  • Human immunodeficiency virus infection 
  • Pneumocystis carinii pneumonia
  • Urticarial vasculitis syndrome with hypocomplementemia, a combination of urticaria, arthralgia, and angioedema, associated with panacinar emphysema
  • Malnutrition-associated elastase-induced peripheral emphysema
  • Sialic acid storage or Salla disease with impaired removal of sialic acid from lysosomes, causing cognitive impairment, ataxia, nystagmus, and basal and centriacinar emphysema
  • Marfan syndrome
  • Polyangiitis with granulomatosis
  • Sjögren disease
  • Sarcoidosis
  • Ehlers-Danlos type IV
  • COVID-19 infection [8][9][10][11][12][13][14]

Epidemiology

Emphysema is associated with high mortality and places a significant burden on healthcare systems due to frequent exacerbations, medical visits, and hospitalizations. According to the World Health Organization, COPD ranks as the fourth leading cause of death worldwide, with 3.5 million deaths in 2021, or about 5% of all global deaths. COPD affects more than 200 million people globally and primarily impacts older adults, as lung tissue damage is often associated with smoking and other age-related risk factors.[15]

Nearly 90% of COPD-related deaths in people younger than 70 occur in low- and middle-income countries.[16] While tobacco smoking causes over 70% of cases of COPD in high-income countries, this condition accounts for 30% to 40% in low- and middle-income countries, due to environmental exposures like household air pollution. Historically, emphysema has been more common in males. However, in developing countries, increased exposure to biomass fuel has led to a more equal distribution of risk between males and females.

Pathophysiology

Chronic inflammation of the distal air spaces, most often caused by harmful exposures like cigarette smoke, underlie the pathophysiology of bullous emphysema.[16] This inflammation leads to the destruction of alveolar walls and the permanent enlargement of air spaces. After an insult upon this barrier, such as by cigarette smoke, the resulting inflammatory response transports antigens to the bronchial-associated lymphatic tissue layer. The macrophages and neutrophils release enzymes such as elastase, which eventually destroy the lung's epithelial barrier. 

As the alveolar walls are damaged, the air spaces become larger and less efficient. Over time, these changes impair gas exchange and reduce airflow due to a loss of elastic recoil in the lungs. Additional features include an increase in goblet cells, mucous gland hyperplasia, fibrosis, and airway collapse due to the loss of alveolar support. These changes contribute to chronic hypoxia and hypercarbia as the disease progresses.

History and Physical

Patients with COPD typically present with progressive shortness of breath, especially on exertion. They may also report a productive cough with thick sputum, often described as a “smoker’s cough,” which is commonly worse in the morning. Other common symptoms include wheezing, fatigue, breathlessness, reduced exercise tolerance, and, in some cases, changes in mental status. Some individuals may be asymptomatic in the early stages, and many do not present until late in the disease, given the gradual onset of symptoms. Patients with giant bullae may also present with chest pain and hemoptysis.

During a physical assessment, signs of hyperinflation may be observed, such as hyperresonance on chest percussion. The examination may also reveal tachypnea, diminished breath sounds, a barrel-shaped chest, wheezing, basilar crackles, or distant heart sounds. In addition, a pronounced P2 heart sound may also be evident, suggesting pulmonary hypertension. Cyanosis or edema in the extremities can occur due to reduced output from the right ventricle or cor pulmonale. Clubbing of the fingers and toes is uncommon unless additional conditions like pulmonary fibrosis, lung cancer, or bronchiectasis are present.[17]

Evaluation

Pulmonary function testing (PFT) is necessary to establish the diagnosis of COPD. PFTs confirm the presence of airflow obstruction, establish the severity, and monitor the progression of the disease.[18] The forced expiratory volume in 1 second/forced vital capacity ratios will typically be less than 0.7 and incompletely reversible after administering an inhaled bronchodilator, as assessed by spirometry following bronchodilator use. Forced vital capacity decreases because of the loss of elastic lung recoil. Additional expected findings are an increased total lung capacity (TLC), residual volume (RV), and functional residual capacity. 

The air trapping identified on PFTs, manifesting as an RV/TLC ratio elevation, corresponds to emphysematous changes found on computed tomography scans of the chest, particularly during expiration.[19] Likewise, TLC can predict hyperinflation and emphysema when increased by more than 120% of predicted in individuals who have a history of smoking.[20] A decrease in the diffusing capacity of the lungs for carbon monoxide will often be present because of the destruction of the lung interstitium. However, normal PFTs are common in individuals with lung disease or symptoms, risk factors, a category classified by the Global Initiative for Obstructive Lung Disease as class 0.[21] Hence, clinical and radiological assessments are essential in these cases to overcome these patients' significant under-estimation and late identification. 

Healthcare professionals should test for α-1 antitrypsin deficiency in patients with emphysema and persistent airflow obstruction.[3] Additional clinical clues that should prompt testing are:

  • Emphysema in a patient aged 45 years or younger or who has never smoked 
  • Predominantly basilar changes on chest radiograph in a patient with emphysema
  • Patients with emphysema and a family history of emphysema or liver disease
  • Adult-onset asthma that fails to improve with bronchodilators 
  • Current findings or a history of panniculitis
  • Patients with emphysema and unexplained chronic liver disease

Patients with suspected COPD undergo plain chest radiographs, which often reveal a flattened diaphragm because of hyperinflation. Bullae appear as radiolucent areas surrounded by thin, curved, white, or light-colored lines representing interlobar fissures. As the disease progresses, prominent hilar vascular markings and cardiomegaly may be evident.[22] Computed tomography (CT) scan of the chest is more sensitive for detecting COPD than chest radiography. A CT scan of the chest is useful when clinicians suspect a complication of COPD or an alternative diagnosis like pneumonia, pneumothorax, giant bullae, thromboembolic disease, or lung cancer, or if a lung cancer screen is appropriate.[23][24][25] Giant bullae are typically evident on chest radiographs. However, they may be difficult to differentiate from a pneumothorax. A CT scan of the chest is helpful in these circumstances. 

To evaluate for other potential etiologies of dyspnea, patients should undergo a complete blood count, serum electrolytes and kidney function, thyroid stimulating hormone level, and plasma brain natriuretic peptide (BNP) or N-terminal pro-BNP to assess for anemia, kidney disease, thyroid disorders, or heart failure.  Electrocardiography may show right axis deviation, right ventricular hypertrophy, or right atrial hypertrophy. Expected findings due to COPD may be increased hemoglobin and hematocrit due to a reactive erythrocytosis secondary to chronic hypoxia. In addition, eosinophilia can indicate a type II inflammation phenotype and overlap with asthma.[26] The eosinophil count can serve as a potential biomarker and assist in stratifying patients into treatable groups.[27]

Patients may have an elevated serum bicarbonate level due to metabolic compensation for respiratory acidosis. Vitamin D levels have been studied extensively in individuals with COPD and reveal that severe vitamin D deficiency can predict frequent exacerbation and hospitalizations.[28][29] Hence, clinicians should assess vitamin D levels in individuals with emphysema, especially those treated with corticosteroids or with an increased risk of bone disease.[30][31] Echocardiography helps to assess right ventricular systolic pressures and estimate the presence of pulmonary hypertension.[32] In addition, clinicians can estimate pulmonary artery pressure by measuring the pulmonary artery (PA) to the aorta (A) ratio on a chest CT scan. A PA/A ratio greater than 1 indicates pulmonary hypertension.[33]

In addition, clinical assessment classification, based on indexes such as the Body Mass Index Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index, helps predict mortality and risk of hospitalization. Clinicians calculate the BODE index based on the body mass index, forced expiratory volume in 1 second, the Medical Research Council dyspnea score, and six-minute walk distance.[34] The COPD Assessment Test score is a good measure of the impact of COPD on a patient's life, particularly in response to rehabilitation or after exacerbations. A decrease in score of 2 points is a clinically significant improvement concerning a patient's health status and symptoms.[35]

Treatment / Management

Chronic Medical Therapy for Non α-1 Antitrypsin Deficiency Bullous Emphysema 

Chronic therapy includes several interventions similar to those used to manage COPD without bullous emphysema.[36][37] Pulmonary rehabilitation improves patients' quality of life and pulmonary function while decreasing healthcare utilization through exercise training, education, and behavioral change. Clinicians base chronic inhaled therapy on the classification of disease and symptoms outlined by the most recent Global Initiative for Chronic Obstructive Lung Disease guidelines.[36](B3)

Initially, all patients should receive a short-acting β-agonist (SABA) such as albuterol for acute shortness of breath and bronchodilation. Following the SABA rescue bronchodilator, patients receive a long-acting muscarinic antagonist (LAMA) and continue the SABA as needed or use a long-acting β-agonist (LABA)-LAMA combination with a SABA as needed based on their symptom severity. Patients with poor symptom control, with at least 1 hospitalization, 2 or more moderate exacerbations over the previous year, or high peripheral eosinophil levels may require inhaled corticosteroids in addition to the LAMA-LABA combination. See StatPearl's companion topics, "Chronic Obstructive Pulmonary Disease and Emphysema'" for further discussion regarding medication management of COPD. Long-term oxygen is a possible add-on therapy if the pO2 is below 55 mm Hg or the oxygen saturation is less than 88% on a 6-minute walk test. For emphysema due to α-1 antitrypsin deficiency, clinicians use augmentation therapy.[38]

Preventive Care

Smoking cessation is of critical importance to combat disease progression and decrease mortality. Necessary vaccinations for patients with COPD include the following:

  • Annual influenza vaccine
  • Pneumococcal vaccine based on local guidelines. In the United States and Canada, the current guidelines are the pneumococcal conjugate vaccine (PCV) 21, except for residents of the Navajo Nation or individuals who reside in the Western United States and Canada who have substance use disorder or who experience homelessness. These patients should receive PCV20 or PCV15, followed by the pneumococcal polysaccharide vaccine (PPSV23) due to the lack of serotype 4 in PCV21. Further guidelines regarding recommendations for revaccinations and patients who have previously received PPSV23 are available through the United States Centers for Disease Control at Expanded Recommendations for Use of Pneumococcal Conjugate Vaccines Among Adults Aged ≥50 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024. 
  • Pertussis
  • COVID-19
  • Respiratory syncytial virus in those aged 60 or older with COPD
  • Shingles or herpes zoster

Many patients with COPD will experience pulmonary cachexia, a body mass index of 20 kg/m2 or less, or a weight below the 90% percentile of the patient's ideal body weight, secondary to the increased metabolic demands of the increased work of breathing. Patients exhibiting these findings will require nutritional support.[39]

Acute Exacerbations

Patients experiencing an acute exacerbation should receive oxygen titrated to an oxygen saturation of 88% to 92%, albuterol-ipratropium, and steroids. Systemic glucocorticoid therapy with a short 5-day course of prednisone provides benefits. Patients with any 2 of the following: increased dyspnea, increased sputum production, viscosity, or purulence, plus an additional risk factor for a poor outcome, also warrant antibiotic therapy. Patients in the hospital are frequently monitored with arterial blood gas to assess for carbon dioxide retention. Understanding potential triggers, like respiratory infections, is also important in managing acute and preventing future COPD exacerbations.

Additional Interventions

Following smoking cessation and optimization of medical therapy, patients who remain symptomatic may require surgical intervention. The general indications include moderate or severe dyspnea, giant bullae, and complications such as pneumothorax, infection, and hemoptysis. Where medical management is inadequate, surgical interventions such as lung volume reduction surgery (LVRS), bullectomy,  and lung transplantation are necessary.[40] Surgeons remove one or more giant bullae by thoracotomy or video-assisted thoracoscopic surgery. LVRS involves a wedge excision of emphysematous tissue.

Experts believe reducing the size of hyperinflated lungs improves expiratory airflow in the non-diseased lungs. Study results reveal that elastic recoil of the lungs may improve after LVRS, which improves the expiratory airflow in the lungs. Affected patients must meet extensive criteria before undergoing LVRS, including notable airflow obstruction on spirometry, evidence of air trapping on lung volume measurements, and CT findings of heterogeneously distributed emphysema.[41][42]

A more recent minimally invasive treatment, using a one-way valve, placed via bronchoscopy, results in lung volume reduction by allowing trapped air and secretions within a lobe to escape but no new air or secretions to re-enter. Indications for the procedure are evidence of emphysema on CT scan with intact lobar fissures, progressive dyspnea as indicated by a Modified Medical Research Council of 2 or more, smoking cessation of 4 months or more, severe airflow obstruction measured on PFTS as an forced expiratory volume in 1 second (FEV1) less than 45% with air trapping as evidenced by an RV of 150% to 170%, and a 6-minute walk test of at least 100 meters.

Contraindications for bronchoscopic valve placement include obesity or a body mass index of more than 35 kg/m2,  congestive heart failure with an ejection fraction of less than 40%, prior thoracic surgery, limited mobility or a 6-minute walk test of fewer than 100 meters, severe hypoxic or hypercapnic respiratory failure with a partial pressure of oxygen less than 45 mm Hg or partial pressure of carbon dioxide in arterial blood greater than 60 mm Hg, active infection, and a severely reduced FEV1 of less than 15%. Patients undergoing these treatments have shown a 100 to 200 mL improvement in their FEV1 and subjective symptoms due to decreased air trapping. However, the risk of pneumothorax is 25% to 30 %.[43]  

Differential Diagnosis

The following list includes the potential differential diagnoses for bullous emphysema:

  • Asthma
  • Bronchiectasis
  • Idiopathic bullous lung disease
  • Bullous lung disease due to human immunodeficiency virus infection
  • Bullous lung disease due to intravenous drug use
  • α-1 antitrypsin deficiency
  • Birt-Hogg-Dubé syndrome
  • Malignancy
  • Lymphangioleiomyomatosis
  • Chronic bronchitis
  • Airway obstruction
  • Heart failure
  • Tuberculosis
  • Interstitial lung disease
  • Thromboembolic disease
  • Pulmonary Langerhans cell histiocytosis [38][39][40]

Complications

Complications related to bullous emphysema arise from both the disease and treatment. The following list includes potential complications related to bullous emphysema:

  • Pneumothorax
  • Pneumonia and other respiratory infections
  • Respiratory failure
  • Cor pulmonale
  • Pulmonary hypertension
  • Myocardial infarction
  • Osteoporosis due to glucocorticoids and inactivity
  • Muscle weakness
  • Cachexia
  • Anxiety and depression
  • Complications due to LVRS include death, arrhythmia, air leak, deep vein thrombosis, pulmonary embolism, and wound infection [41][42][43][44][45][46][47][48][49]

Deterrence and Patient Education

Bullous emphysema, a form of COPD characterized by the irreversible destruction of alveolar structures resulting in the formation of bullae, places a significant burden on healthcare systems and dramatically impacts patients' lives. Patient education plays a vital role in preventing and managing bullous emphysema. Smoking cessation remains the most important modifiable intervention and should be strongly encouraged. Educating patients about the risks of environmental and occupational exposures, including air pollutants and biomass smoke, is also essential in reducing disease progression.

Clinicians should educate patients about the nature of their condition and the associated risks, including pneumothorax, heart failure, myocardial infarction, pneumonia, and increased mortality. Awareness of these potential complications helps patients appreciate the need for recommended diagnostic evaluations and highlights the importance of consistent medication use and preventive care. Reinforcing the value of maintenance therapies, routine vaccinations, pulmonary rehabilitation, and regular follow-up can empower patients to participate in their treatment actively, ultimately improving outcomes and reducing the likelihood of serious complications. Clinicians should counsel patients on recognizing early signs of worsening disease—such as increased dyspnea, purulent sputum, chest discomfort, or hemoptysis—and when to seek medical care. Following smoking cessation and medication optimization, patients with persistent symptoms or giant bullae may require surgical intervention.

Enhancing Healthcare Team Outcomes

Bullous emphysema is a form of COPD characterized by airflow limitation due to irreversible destruction and enlargement of alveolar spaces beyond the terminal bronchioles. This structural damage can lead to the formation of bullae within the lung parenchyma. Clinically, patients may present with progressive dyspnea, wheezing, productive cough, and exercise intolerance, though symptoms may be insidious. Physical findings include signs of hyperinflation, diminished breath sounds, and possible indicators of right heart strain. Diagnosis is typically confirmed with pulmonary function testing, supported by imaging and lab studies to exclude other causes of dyspnea. CT imaging is particularly valuable in distinguishing bullae from pneumothorax or evaluating for complications. Management focuses on smoking cessation and optimizing medical therapy. In patients with persistent symptoms or giant bullae, surgical options such as lung volume reduction surgery, bullectomy, or bronchoscopic one-way valve placement are potential options.

Effective management of bullous emphysema requires a coordinated, multidisciplinary approach in which each healthcare professional contributes specific skills and collaborates to deliver patient-centered, evidence-based care. Advanced clinicians must thoroughly understand the pathophysiology, diagnostic criteria, and treatment options for bullous emphysema, including the ability to interpret pulmonary function tests and imaging to determine disease severity and implement appropriate therapy. Nurses play a key role in patient education, symptom monitoring, and early recognition of exacerbations or complications such as pneumothorax while supporting adherence to medication and oxygen therapy.

Pharmacists contribute by ensuring appropriate medication management, identifying potential drug interactions, and counseling patients on the correct use of inhalers and other therapies. Respiratory therapists are instrumental in delivering pulmonary rehabilitation and teaching breathing techniques that improve lung efficiency and quality of life. Each healthcare team member must communicate findings clearly and consistently with the broader care team to inform timely decision-making. Interprofessional communication is essential for coordinating care, especially when considering surgical interventions.

A successful strategy includes regular team meetings, shared electronic health records, and clearly defined care pathways. Care coordination ensures continuity across settings—from outpatient clinics to surgical consults and post-discharge follow-up—helping to prevent hospital readmissions and improve long-term outcomes. When healthcare teams align their expertise and maintain open communication, they enhance patient safety, improve treatment outcomes, and empower patients to participate in their care actively.

Media


(Click Image to Enlarge)
<p>Bilateral Bullous Emphysema, Computed Tomography. This computed tomography image shows bilateral bullous emphysema.</p>

Bilateral Bullous Emphysema, Computed Tomography. This computed tomography image shows bilateral bullous emphysema.

Contributed by S Bhimji, MD

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