Pulmonary Medicine

Bronchiolitis (respiratory bronchiolitis, acute bronchiolitis, constrictive or obliterative bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis, diffuse aspiration bronchiolitis, mineral dust airway disease)

What every physician needs to know:

Bronchiolitis, also referred to as bronchiolar disease, is a generic term used to describe inflammation of the bronchioles, with or without scarring. Bronchiolitis, a common lesion in the lung, is encountered in a variety of clinical contexts. Several histologic types of bronchiolitis ("primary" bronchiolar diseases) are recognized and have varying degrees of specificity with respect to etiology.

Bronchiolitis is small airway involvement in interstitial lung diseases like respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), hypersensitivity pneumonitis, cryptogenic or secondary organizing pneumonia (OP), sarcoidosis, and idiopathic pulmonary fibrosis (IPF). In most cases, RB-ILD and DIP are forms of smoking-related interstitial lung diseases.

Hypersensitivity pneumonitis is caused by repeated inhalation of sensitizing agents, and bronchiolitis is commonly seen in patients with this disorder. Organizing pneumonia (also called bronchiolitis obliterans organizing pneumonia, or BOOP), is a nonspecific injury pattern that can be seen in many clinical contexts, including infections, drug-induced lung disease, and connective tissue diseases.

Bronchiolar involvement can also be seen in predominantly large airway diseases like bronchiectasis, chronic bronchitis, and cystic fibrosis.

Classification:

Primary bronchiolar diseases include:

  • respiratory bronchiolitis

  • acute bronchiolitis

  • constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans)

  • follicular bronchiolitis

  • diffuse panbronchiolitis

  • diffuse aspiration bronchiolitis

  • mineral dust airway disease

Are you sure your patient has bronchiolitis? What should you expect to find?

The clinical presentation of bronchiolitis is nonspecific; it varies somewhat according to the type of bronchiolitis. In general, the presenting symptoms are cough and exertional dypsnea. The onset of symptoms may be acute, as in acute bronchiolitis, or insidious, as in constrictive bronchiolitis. Extrapulmonary and constitutional symptoms may be present in cases of bronchiolitis that are due to infection, as well as in patients with underlying systemic illness, such as connective tissue diseases. Patients with bronchiolitis may be asymptomatic, presenting primarily for evaluation of abnormal chest imaging findings or pulmonary function test results (e.g., some patients with respiratory bronchiolitis).

Beware: there are other diseases that can mimic bronchiolitis:

Because the clinical presentation associated with bronchiolitis is nonspecific and variable, the differential diagnosis is broad; it includes infections, chronic obstructive pulmonary disease, asthma, and various forms of interstitial lung disease.

How and/or why did the patient develop bronchiolitis?

Clinical context is a crucial consideration in diagnosing bronchiolitis. For example, progressively worsening dyspnea and airflow obstruction in patients with solid organ or hematopoietic stem cell transplantation suggest the diagnosis of transplant-related bronchiolitis obliterans (or obliterative bronchiolitis), particularly if pulmonary infiltrates are not seen on chest imaging. Transplant-related bronchiolitis obliterans appears to be the result of multiple factors, including allograft rejection, ischemia-reperfusion injury, infections, and gastroesophageal reflux. A similar phenomenon of progressive airflow obstruction can be encountered in patients with connective tissue diseases like rheumatoid arthritis, in whom autoimmunity, infections, drugs, and other factors contribute to the bronchiolar disease.

Other forms of bronchiolitis also have characteristic epidemiologic associations, such as young age (acute bronchiolitis), smoking (respiratory bronchiolitis), immunodeficiency diseases (follicular bronchiolitis), Asian ancestry (diffuse panbronchiolitis), and inorganic dust exposure (mineral dust airway disease).

Which individuals are at greatest risk of developing bronchiolitis?

Bronchiolitis may assume a variety of clinical presentations and may present at any age.

  • Acute bronchiolitis, which is usually due to respiratory viral infections, is typically encountered in infants and children. It is the leading cause of hospitalization in infants.

  • Respiratory bronchiolitis, which occurs in adults, is nearly always associated with smoking. A small fraction of cases is related to occupational or environmental fume exposures.

  • Constrictive bronchiolitis is commonly encountered as "bronchiolitis obliterans syndrome" in patients with solid organ or hematopoietic stem cell transplantation who experience progressive respiratory symptoms. Constrictive bronchiolitis may also be seen as one form of pulmonary involvement in patients with underlying connective tissue diseases, such as rheumatoid arthritis.

  • Follicular bronchiolitis is usually seen in patients with connective tissue diseases, immunodeficiency disorders, or chronic infections.

  • Diffuse panbronchiolitis is an unusual form of bronchiolitis described mainly in the Asian population (particularly in the Japanese).

  • Diffuse aspiration bronchiolitis is typically seen in middle-aged or older adults who have risk factors for aspiration, such as a neurologic disorder or gastroesophageal reflux disease (GERD). The aspiration may be clinically occult.

  • Mineral dust airway disease is caused by inhalation of inorganic dusts, including silica, silicates, asbestos, iron oxide, aluminum oxide, talc, mica, and coal. The disorder is primarily occupation-related.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

In the context of an acute respiratory illness encountered in an infant or child, blood tests and sputum cultures may confirm the presence of a viral respiratory tract infection and enable the diagnosis of acute bronchiolitis. In general, routine laboratory studies are unhelpful in diagnosing bronchiolitis, but they may assist in establishing the clinical context or underlying disease of which the bronchiolitis may be a manifestation. For example, serologies may suggest the presence of an underlying connective tissue disease in a patient suspected of having constrictive bronchiolitis.

What imaging studies will be helpful in making or excluding the diagnosis of bronchiolitis?

In most cases of suspected bronchiolitis, a high-resolution chest CT scan is necessary to define the pattern of radiographic abnormalities, their distribution, and associated findings, such as intrathoracic lymphadenopathy and pleural effusion. Routine chest radiography may reveal abnormal findings, but plain films may appear normal in patients with bronchiolar disease. A chest x-ray or CT scan may reveal that the suspected bronchiolitis is associated with an underlying interstitial pulmonary process or large airway disease.

Some forms of bronchiolitis are associated with characteristic imaging findings.

  • High-resolution chest CT imaging in patients with respiratory bronchiolitis demonstrates centrilobular micronodules of ground-glass attenuation ( Figure 1).

  • CT imaging in constrictive bronchiolitis primarily shows patchy air trapping, evident as a mosaic pattern, a patchwork of regions of differing attentuation, that is accentuated on expiratory views. (Figure 2) ( Figure 3).

Figure 1.

High-resolution CT scan of the chest of a 56-year-old smoker reveals numerous centrilobular nodules of ground-glass attenuation throughout both lungs.

Figure 2.

Inspiratory view on high-resolution CT of a 66-year-old woman with cryptogenic constrictive bronchiolitis reveals a subtle mosaic pattern with regional heterogeneity in attenuation.

Figure 3.

Expiratory view of the same patient accentuates the mosaic pattern associated with regional air trapping because of constrictive bronchiolitis.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of bronchiolitis?

Pulmonary function testing is useful in evaluating patients with suspected bronchiolitis, particularly those with chronic forms of bronchiolitis. In most cases, an obstructive pattern is encountered, but pulmonary function tests may be normal, particularly in the presence of mild bronchiolar disease.

What diagnostic procedures will be helpful in making or excluding the diagnosis of bronchiolitis?

In some cases of bronchiolitis, the clinical context and characteristic high-resolution chest CT findings may suffice for diagnosing the underlying bronchiolar disease, such as respiratory bronchiolitis in a smoker. A mosaic pattern with evidence of patchy air trapping and airflow obstruction seen on pulmonary function testing suggests the presence of constrictive bronchiolitis. In patients with solid organ or hematopoietic stem cell transplantation, these features are generally sufficient to diagnose transplant-related bronchiolitis obliterans in the absence of any other cause to explain such findings.

In other forms of bronchiolitis, such as follicular bronchiolitis, the chest CT findings are nonspecific, and lung biopsy is generally needed to distinguish bronchiolar disease from other lung disorders. (Figure 4, Figure 5, Figure 6, Figure 7, Figure 8)

Figure 4.

High-resolution image (inspiration) of a fifty-year-old woman with hypersensitivity pneumonitis demonstrates diffuse ground-glass opcacities with several scattered regions of air trapping.

Figure 5.

Histopathologic features of respiratory bronchioltis characterized by accumulation of pigmented macrophages within the respiratory bronchioles and adjacent alveoli

Figure 6.

Histopathology of acute bronchiolitis characterized by dense peribronchiolar infiltrate of acute and chronic inflammatory cells associated with an intraluminal exudate rich in neutrophils

Figure 7.

Histopathology of constrictive bronchiolitis characterized by fibroblast proliferation and stromal edema with associated collagen deposition in the submucosa, resulting in airway luminal constriction

Figure 8.

Histopthology of organizing pneumonia (or BOOP), characterized by intraluminal plugs of proliferating fibroblasts that fill distal airways and peribonchiolar air spaces

When a lung biopsy is required, fiberoptic bronchoscopic biopsy may yield the diagnosis if characteristic histopathologic features are seen; for example, bronchoscopy is sometimes useful in the diagnosis of forms of bronchiolitis like diffuse panbronchiolitis or diffuse aspiration bronchiolitis. In most cases, however, surgical lung biopsy, usually via video-assisted thoracoscopic surgery (VATS), is needed. Surgical lung biopsy is may be needed to confirm the diagnoses of constrictive bronchiolitis, follicular bronchiolitis, respiratory bronchiolitiis, or mineral airways disease, if clinically indicated.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of bronchiolitis?

As described in the previous section, bronchoscopic or surgical lung biopsy may be needed to confirm the presence and the histopathologic pattern of bronchiolitis.

If you decide the patient has bronchiolitis, how should the patient be managed?

Because bronchiolitis may be associated with a wide variety of causes and underlying disorders, the specific type of bronchiolitis and the clinical context should be considered in evaluating management options. In general, treatment approaches include avoidance of exposure to the causative agent, treatment of the underlying systemic disease, and use of specific drugs, including corticosteroids, other immunosuppressives, and macrolides.

  • For acute bronchiolitis, supportive care of the child at home, including ensuring adequate fluid intake and nasal bulb suctioning, may suffice in caring for those with mild illness. Hospitalization is usually required for patients with moderate or severe acute bronchiolitis that manifests in respiratory distress, dehydration, poor feeding, or lethargy. Inpatient management may include oxygen supplementation, intravenous fluid administration, bronchodilators, corticosteroids, antibiotics, and (occasionally) mechanical ventilation.

  • For respiratory bronchiolitis and mineral dust airway disease, the main management strategy is avoidance of additional inhalational exposure to the offending agent--that is, cigarette smoke and inorganic dusts, respectively.

  • Optimal management of constrictive bronchiolitis requires identification of the underlying cause or systemic disease. For patients with bronchiolitis obliterans syndrome, treatment involves intensification of immunosuppressive therapy and use of macrolides. Constrictive bronchiolitis associated with connective tissue diseases is managed with corticosteroids and immunomodulatory agents aimed at the underlying systemic disease. Corticosteroids and immunomodulatory agents are also used in patients for whom the underlying cause of the constrictive bronchiolitis cannot be identified (cryptogenic constrictive bronchiolitis). However, these agents appear to be of limited efficacy.

  • Follicular bronchiolitis is usually treated by managing the underlying condition, that is, the connective tissue disease or immunodeficiency disorder.

  • Macrolide therapy is the treatment of choice for patients with diffuse panbronchiolitis.

  • Diffuse aspiration bronchiolitis is managed with anti-gastroesophageal reflux measures. Fundoplication may be needed to prevent recurrent aspiration In patients who do not respond to non-surgical measures.

What is the prognosis for patients managed in the recommended ways?

Prognosis depends on the type of bronchiolitis:

  • Acute bronchiolitis is usually a self-limited disease that is managed well with supportive therapy.

  • Respiratory bronchiolitis is a common, smoking-related disease that is generally not associated with significant respiratory impairment. Some patients with respiratory bronchiolitis may have associated interstitial lung disease--either so called respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) or desquamative interstitial pneumonia (DIP), which are also smoking-related in most cases. These disorders may result in significant respiratory impairment and, in some instances, may produce respiratory failure.

  • Not uncommonly, constrictive bronchiolitis worsens despite administration of corticosteroids, other immunosuppressive agents, or macrolide therapy. Progressive constrictive bronchiolitis may result in respiratory failure and death in patients who are solid organ or hematopoietic stem cell transplant recipients, in those with a connective tissue disorders, and in those with cryptogenic disease.

  • The prognosis for patients with follicular bronchiolitis is determined by the underlying disease. By itself, follicular bronchiolitis is generally not associated with significant morbidity.

  • Prior to the therapeutic use of macrolide therapy, diffuse panbronchiolitis was characterized by progressive respiratory dysfunction and recurrent bacterial infections, with nearly half of patients succumbing to respiratory failure within five years of diagnosis. Macrolide therapy has improved the prognosis associated with diffuse panbronchiolitis such that the ten-year survival rate is now above 90 percent.

  • Diffuse aspiration bronchiolitis generally does not result in progressive respiratory impairment when it is correctly diagnosed and managed.

  • Mineral dust airway disease is usually diagnosed on lung biopsy and is not associated with significant morbidity.

What other considerations exist for patients with bronchiolitis?

In some patients with bronchiolitis, the bronchiolar disease may represent only a minor component of a broader interstitial lung process, such as hypersensitivity pneumonitis or a large airway disease like bronchiectasis. Evaluation of the clinical context, along with radiologic findings, particularly on high-resolution chest CT, should clarify the issue (Figure 4).

What’s the evidence?

Aerni, MR. "Follicular bronchiolitis in surgical lung biopsies: clinical implications in 12 patients". Respir Med. vol. 102. 2008. pp. 307-12.

A description of twelve patients with follicular bronchiolitis and clinical contexts associated with this bronchiolar disorder.

Ahmad, S, Shlobin, OA, Nathan, SD. "Pulmonary complications of lung transplantation". Chest. vol. 139. 2011. pp. 402-11.

A review of pulmonary complications, including bronchiolitis obliterans syndrome, in lung transplant recipients.

Allen, TC. "Pathology of small airways disease". Arch Pathol Lab Med. vol. 134. 2010. pp. 702-18.

A review of histopathologic features associated with various forms of bronchiolitis.

Barnes, TW, Vassallo, R, Hartman, TE, Tazelaar, HD, Ryu, JH. "Diffuse bronchiolar disease due to chronic occult aspiration". Mayo Clin Proc. vol. 81. 2006. pp. 172-6.

A description of four patients with diffuse aspiration bronchiolitis resulting from recurrent occult aspiration.

Friedlander, AL, Albert, RK. "Chronic macrolide therapy in inflammatory airways diseases". Chest. vol. 138. 2010. pp. 1202-12.

A summary of the current evidence on the use of chronic macrolide therapy for airways diseases.

Pipavath, SJ, Lynch, DA, Cool, C, Brown, KK, Newell, JD. "Radiologic and pathologic features of bronchiolitis". Am J Roentgenol. vol. 185. 2005. pp. 354-63.

A review of imaging characteristics associated with various forms of bronchiolitis.

Ryu, JH, Myers, JL, Swensen, SJ. "Bronchiolar disorders". Am J Respir Crit Care Med. vol. 168. 2003. pp. 1277-92.

A review that describes several forms of primary bronchiolar disorders (bronchiolitis), as well as bronchiolitis associated with interstitial lung disease and large airway diseases.

Ryu, JH, Colby, TV, Hartman, TE, Vassallo, R. "Smoking-related interstitial lung diseases: concise review". Eur Respir J. vol. 17. 2001. pp. 122-32.

A review of the smoking-related interstitial lung diseases, including respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia.

Zorc, JJ, Hall, CB. "Bronchiolitis: recent evidence on diagnosis and management". Pediatrics. vol. 125. 2010. pp. 342-9.

A review of the current evidence pertaining to the diagnosis and management of acute bronchiolitis.
You must be a registered member of Renal and Urology News to post a comment.

Sign Up for Free e-newsletters