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Bronchiolitis Obliterans and Organizing Pneumonia

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Bronchiolitis Obliterans and Organizing Pneumonia

Immunocompromised (bone marrow, lung, renal transplantation)Malignancy: colon, breast, lymphomaBronchial obstruction (lack of mucociliary clearance), that is, lung cancerConnective tissue diseases

Think of the possibility in patients presenting with

Inpatient care may be required.

Prednisone: 1 mg/kg q24h for 1 month, followed by weaning over several months

Typically complete recovery, but individual case management is mandatory.

1.Cottin V, Cordier JF. Cryptogenic organizing pneumonia. Semin Respir Crit Care Med. 2012;33(5):462-475. [View Abstract]2.Marchiori E, Zanetti G, Hochhegger B, et al. Reversed halo sign on computed tomography: state-of-the-art review. Lung. 2012;190(4):389-394. [View Abstract]3.Marchiori E, Irion KL, Zanetti G, et al. Atoll sign or reversed halo sign? Which term should be used? Thorax. 2011;66(11):1009-1010. [View Abstract]4.Drakopanagiotakis F, Paschalaki K, Abu-Hijleh M, et al. Cryptogenic and secondary organizing pneumonia: clinical presentation, radiographic findings, treatment response, and prognosis. Chest. 2011;139(4):893-900. [View Abstract]5.Jara-Palomares L, Gomez-Izquierdo L, Gonzalez-Vergara D, et al. Utility of high-resolution computed tomography and BAL in cryptogenic organizing pneumonia. Respir Med. 2010;104(11):1706-1711. [View Abstract]6.Papakosta D, Manika K, Gounari E, et al. Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia. Respirology. 2014;19(5):748-754. [View Abstract]7.Ye Q, Dai H, Sarria R, et al. Increased expression of tumor necrosis factor receptors in cryptogenic organizing pneumonia. Respir Med. 2011;105(2):292-297. [View Abstract]

Amiodarone toxicity

Acebutolol toxicity

Amphotericin B

  • Bleomycin
  • Carbamazepine
  • Cephalosporins
  • Gold
  • Minocycline
  • Nitrofurantoin
  • Phenytoin
  • Sulfamethoxypyridazine
  • Sulfasalazine
  • Ticlopidine

Bleomycin

Carbamazepine

Cephalosporins

Gold

Minocycline

Nitrofurantoin

Phenytoin

Sulfamethoxypyridazine

Sulfasalazine

Ticlopidine

  • Freebase cocaine pulmonary toxicity
  • Overdose of L-tryptophan

Freebase cocaine pulmonary toxicity

Overdose of L-tryptophan

  • Chronic infectious pneumonia
  • Malaria
  • Chlamydia
  • Legionella
  • Mycoplasma
  • Pneumocystis
  • Cryptococcus

Chronic infectious pneumonia

Malaria

Chlamydia

Legionella

Mycoplasma

Pneumocystis

Cryptococcus

  • BOOP itself is an autoimmune connective tissue disorder, so autoimmune connective tissue disorders confer a higher risk of acquiring the disease.

BOOP itself is an autoimmune connective tissue disorder, so autoimmune connective tissue disorders confer a higher risk of acquiring the disease.

  • Sj ¶gren syndrome
  • Polymyositis
  • Scleroderma
  • Essential mixed cryoglobulinemia
  • Wegener granulomatosis

Sj ¶gren syndrome

Polymyositis

Scleroderma

Essential mixed cryoglobulinemia

Wegener granulomatosis

  • Cystic fibrosis
  • Bronchopulmonary dysplasia
  • Renal failure
  • Congestive heart failure (CHF)
  • Adult respiratory distress syndrome

Cystic fibrosis

Bronchopulmonary dysplasia

Renal failure

Congestive heart failure (CHF)

Adult respiratory distress syndrome

  • Chronic eosinophilic pneumonia
  • Hypersensitivity pneumonitis
  • Histiocytosis X
  • Sarcoidosis
  • Pneumoconioses

Chronic eosinophilic pneumonia

Hypersensitivity pneumonitis

Histiocytosis X

Sarcoidosis

Pneumoconioses

Diagnosis

  • Flulike illness that lasts 4-10 weeks or longer. Most have been treated with antibiotics without success.
  • Fatigue, fever, and weight loss
  • Dry cough
  • Dyspnea may be severe.
  • Bilateral crackles

History

  • Fatigue
  • Malaise
  • Fever/chills
  • Weight loss
  • Dry cough
  • Dyspnea may be severe.

Physical Exam

  • Hypoxia
  • Cyanosis
  • Respiratory distress
  • Bilateral crackles and/or
  • Wheezing
  • Dry cough
  • Shortness of breath
  • Rarely: hemoptysis, respiratory distress

Differential Diagnosis

  • Usual interstitial pneumonitis
  • Noninfectious diseases
  • Tuberculosis
  • Sarcoidosis
  • Histoplasmosis
  • Berylliosis
  • Goodpasture syndrome
  • Neoplasm
  • Polyarteritis nodosa
  • Systemic lupus erythematosus
  • Wegener granulomatosis
  • Sj ¶gren syndrome
  • Chronic eosinophilic pneumonia
  • Cryptogenic bronchiolitis

Diagnostic Tests & Interpretation

  • May have normal or nonspecific laboratory findings
  • Leukocytosis with a normal differential
  • Elevated ESR
  • Eosinophilia
  • Anemia
  • If secondary to autoimmune process, may have elevated levels of antinuclear antibodies (ANA), rheumatoid factor (RF), anti-SSA/Ro, anti-SSB/La, anti-Jo, etc.
  • Negative cultures
  • Negative serology for Mycoplasma, Coxiella, Legionella, psittacosis, and fungus
  • Negative viral studies
  • CXR: often appears more normal than the physical examination CXR may show bilateral patchy alveolar opacities (typical pattern), often in the middle or upper lung area, a ground glass pattern that may have air bronchograms.CXR can also reveal a solitary focal nodule or mass known as a focal pattern (1)[B].
  • Throughout the disease, new infiltrates may appear or may seem to migrate.
  • Effusions and cavitary lesions are rare on x-ray.
  • Patients with linear opacities at lung bases may have a poorer prognosis.
  • CT scans more accurately define the distribution and extent of the patchy alveolar opacities with areas of hyperlucency. Findings are commonly described as a "reversed halo sign"¯ or "Atoll sign,"¯ a focal round area of ground glass attenuation; however, this is a nonspecific finding (2,3)[A].
  • Up to 90% of CT scans may show airspace consolidation with air bronchograms.
  • Pulmonary function shows a restrictive/obstructive pattern.
  • Flow-volume loop shows terminal airway obstruction.
  • The involved area may seem to migrate.
  • Ventilation-perfusion ratio scan: matched patchy defects
  • CXR may show bilateral patchy alveolar opacities (typical pattern), often in the middle or upper lung area, a ground glass pattern that may have air bronchograms.
  • CXR can also reveal a solitary focal nodule or mass known as a focal pattern (1)[B].

CXR may show bilateral patchy alveolar opacities (typical pattern), often in the middle or upper lung area, a ground glass pattern that may have air bronchograms.

CXR can also reveal a solitary focal nodule or mass known as a focal pattern (1)[B].

  • In one study, open lung biopsy established the correct diagnosis in 1/3 of patients (4)[B].
  • Transbronchial biopsy has yielded a correct diagnosis in 2/3 of cases (4,5)[B].
  • It may be wise to use a trial of steroids as a diagnostic trial, although not all would agree.
  • If a diagnostic trial is successful, be prepared to treat the patient for at least 1 year.
  • Bronchoalveolar lavage (BAL) fluid in patients with BOOP have shown larger amounts of natural killer cells, natural killer T-like cells, Fas and tumor necrosis factor receptor expression indicating cytotoxicity and local inflammation (5,6)[C]. In one specific study, the most frequent BAL profile was mixed alveolitis with lymphocytic predominance, a CD4/CD8 index of 0.4, and foamy macrophages, which was shown to be specific (88.8%) but not sensitive (4)[C].
  • Intraluminal fibrosis of distal airspaces is the major pathologic feature.
  • Fibroblasts and plugs of inflammatory cells and loose connective tissue fill these distal airways, known as Masson bodies.
  • Inflammatory cells are mainly lymphocytes and plasma cells.
  • Interstitial fibrosis is present.
  • Plugs of edematous granulation tissue in the terminal and respiratory bronchioles and alveolar ducts do not cause permanent damage.

Treatment

General Measures

  • Monitor blood gases or pulse oximetry.
  • Oxygen, as necessary

Medication

  • 1 mg/kg (up to 60 mg/day) for 1-3 months, then 40 mg/day for 3 months, then 10-20 mg/day for up to 1 year
  • May consider a 6-month-only taper or alternate day dosing for 1 year to limit steroid exposure
  • Increase length of taper for patients on long-term therapy to avoid precipitating addisonian crisis.
  • Treatment may be needed for ≥1 year.
  • In one study, the best response to corticosteroid therapy was seen in individuals younger than 35 years of age, nonsmokers, and with morphologic features (large bronchial plugs, mild inflammatory reaction) and immunohistochemical markers (presence of collagen IV, absence of collagen III, CD-68-positive cells and positive VEGF) (7)[B].
  • Contraindications: Refer to the manufacturer's literature.
  • Precautions: Be aware of the patient's Mantoux status and history of peptic ulcer disease. Long-term steroid treatment is associated with significant adverse effects, including Cushing syndrome, fluid retention, osteoporosis, hyperkalemia, and poor wound healing.
  • Steroids other than prednisone may be used.
  • Prescribe antimicrobials if the original infection is persistent. The proper choice depends on the pathogen.
  • Anecdotal use of inhaled triamcinolone and cyclophosphamide has been reported.
  • Macrolide antibiotics have also been used for their anti-inflammatory properties; however, not employed in most cases (4)[C]

Issues for Referral

Ongoing Care

Follow-up Recommendations

  • Frequent visits, weekly at first
  • Prednisone must be continued because of the chance of relapse.
  • Monitor the lung disease and the side effects of prednisone therapy: Annual Mantoux/purified protein derivativeMonthly CBCFunduscopic examination every 3-6 monthsSerial dual energy x-ray absorptiometry (DEXA) scans for osteoporosis
  • Smoking cessation is encouraged. Advice and information about smoking cessation interventions should be provided (i.e., counseling, nicotine replacement, medications, etc.).
  • Annual Mantoux/purified protein derivative
  • Monthly CBC
  • Funduscopic examination every 3-6 months
  • Serial dual energy x-ray absorptiometry (DEXA) scans for osteoporosis

Annual Mantoux/purified protein derivative

Monthly CBC

Funduscopic examination every 3-6 months

Serial dual energy x-ray absorptiometry (DEXA) scans for osteoporosis

Diet

Patient Education

  • Compliance: Emphasize the need to continue prednisone because of the chance of a relapse.
  • Recurrence in up to 1/3 who do not complete full steroid treatment.

Prognosis

Complications

  • Bronchiectasis
  • Most people recover completely without permanent sequelae if full course of steroids completed.
  • Death occurs in up to 7% but usually in individuals who are elderly or have pre-existing comorbid conditions.

References

Additional Reading

  • Cordier JF, Loire R, Brune J. Idiopathic bronchiolitis obliterans organizing pneumonia. Definition of characteristic clinical profiles in a series of 16 patients. Chest. 1989;96(5):999-1004. [View Abstract]
  • Drakopanagiotakis F, Polychronopoulos V, Judson MA. Organizing pneumonia. Am J Med Sci. 2008;335(1):34-39. [View Abstract]
  • Limper AH. Chemotherapy-induced lung disease. Clin Chest Med. 2004;25(1):53-64. [View Abstract]
  • Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr. 2008;20(3):272-278. [View Abstract]
  • M ¼ller NL, Staples CA, Miller RR. Bronchiolitis obliterans organizing pneumonia: CT features in 14 patients. AJR Am J Roentgenol. 1990;154(5):983-987. [View Abstract]
  • Ruth-Sahd LA, White KA. Bronchiolitis obliterans organizing pneumonia. Dimens Crit Care Nurs. 2009;28(5):204-208. [View Abstract]
  • Schlesinger C, Koss MN. The organizing pneumonias: an update and review. Curr Opin Pulm Med. 2005;11(5):422-430. [View Abstract]
  • White KA, Ruth-Sahd LA. Bronchiolitis obliterans organizing pneumonia. Crit Care Nurse. 2007;27(3):53-66; quiz 67. [View Abstract]

See Also

Codes

ICD10

  • J84.89 Other specified interstitial pulmonary diseases
  • J44.9 Chronic obstructive pulmonary disease, unspecified

ICD09

  • 516.8 Other specified alveolar and parietoalveolar pneumonopathies
  • 491.8 Other chronic bronchitis
  • 516.34 Respiratory bronchiolitis interstitial lung disease

SNOMED

  • 129458007 Bronchiolitis obliterans organizing pneumonia (disorder)
  • 40100001 Obliterative bronchiolitis (disorder)
  • 233723008 Bronchiolitis obliterans with usual interstitial pneumonitis (disorder)

Clinical Pearls

  • BOOP is a restrictive problem that is completely reversible.
  • Major risk factors for BOOP include immunosuppression and smoking.
  • When diagnosing BOOP, one should perform an autoimmune workup.
  • The classic CT finding of BOOP is the "reversed halo sign"¯ also known as "Atoll sign."¯
  • BOOP treatment is a prolonged course of corticosteroids.