Complications of Pneumonia: Postinfective Bronchiolitis Obliterans

Complications of Pneumonia: Postinfective Bronchiolitis Obliterans

Paul C. Stillwell, MD, FAAP, and Deborah R. Liptzin, MD, MS, FAAP

Introduction/Etiology/Epidemiology

•Obliterative bronchiolitis, or bronchiolitis obliterans, is obliteration of the small brochiolar airways with fibrinoproliferative material.

•It occurs in a variety of settings (Box 65-1).

—In North America, it occurs infrequently after viral infection and more commonly after lung transplantation or hematopoietic stem cell transplantation.

—In indigenous populations, it is commonly seen after viral infections (postinfectious bronchiolitis obliterans).

Box 65-1. Underlying Systemic Disease or Trigger for Development of Obliterative Bronchiolitis

Autoimmune disease	Posttransplant causes
Rheumatoid arthritis	Hematopoietic stem cell transplant
Sjogren syndrome
Systemic lupus erythematosus	Lung transplant
Inhalational agents	Aspiration
Sulfur mustard
Nitrogen oxides	Stevens-Johnson syndrome
Mold
Avian antigens
Others
Infections
Adenovirus
Measles
Mycoplasma
Others

Clinical Features

•Signs of obliterative bronchiolitis are inspiratory crackles, barrel chest, hypoxemia, and tachypnea.

•Symptoms of obliterative bronchiolitis are cough, dyspnea, and wheezing.

•Signs and symptoms may be subtle. Dyspnea is often very prominent, even with minimal exertion.

Diagnostic Considerations

•The standard of reference for diagnosis is lung biopsy; however, disease can be patchy and missed at biopsy (particularly transbronchial biopsy).

•The pathologic process causes the airways to be narrowed or completely obliterated; airway fibrosis will be present.

•At pulmonary function testing, obstruction and air trapping will be found, typically with minimal postbronchodilator improvement (Figure 65-1).

•Chest radiographs show variable, nonspecific findings that range from patchy to diffuse air space opacity (Figure 65-2). Computed tomographic (CT) findings are more specific and include air trapping, mosaic perfusion, and vascular attenuation, with or without bronchiectasis (Figure 65-3).

—Mosaic perfusion appears as areas of decreased attenuation that are darker on CT images, due to decreased perfusion.

—Vascular attenuation appears as loss of blood vessel visibility in areas of decreased lung perfusion.

•Lung transplant recipients with a clinically significant change in pulmonary function test results (obstruction) without a lung biopsy have bronchiolitis obliterans syndrome.

Treatment

•Treatment is based on expert opinion and on adult trials for bronchiolitis obliterans syndrome.

•Monitor the patient for hypoxemia with exercise and at night, and treat as needed.

•Monitor the patient for pulmonary hypertension, and treat as needed.

•Consult with a pediatric pulmonologist with expertise in children’s interstitial and diffuse lung disease.

•Common medication regimens are listed in Table 65-1.

•Adult studies also suggest fluticasone, azithromycin, and montelukast.

•If the patient also has bronchiectasis, airway clearance and early antibiotics should be initiated for a cough.

Figure 65-1. Pulmonary function testing demonstrates severe obstruction in obliterative bronchiolitis. ex = expiratory, FEF25%-75% = forced expiratory flow between 25% and 75% of vital capacity, FEV 1 = forced expiratory volume in 1 second, F/V = flow-volume, FVC = forced vital capacity, in = inspiratory, PEF = peak expiratory flow, Ref = reference, VBe = volume backextrapolation, Vol = volume.

Figure 65-2. Obliterative bronchiolitis in a 10-year-old boy with leukemia. Frontal chest radiograph demonstrates nonspecific bilateral, diffuse air space opacity. Note the central line overlying the left brachiocephalic vein.

Figure 65-3. Obliterative bronchiolitis in a patient after having Stevens-Johnson syndrome. Axial chest computed tomographic image demonstrates regions of mosaic perfusion (typical of obliterative bronchiolitis) scattered between areas of normal lung. The mosaic perfusion areas can be recognized by the well-defined margins and low attenuation due to decreased visualization of the normal vascular structures.

Table 65-1. Treatment for Obliterative Bronchiolitis
Treatment	Dose	Interval
Methylprednisolone	IV 10–30 mg/kg for 3 d	Every month
IV immunoglobulin	IV 2 g/kg for 1 d	Every month
Azithromycin	10 mg/kg by mouth (maximum, 500 mg)Alternate dosing:18.0–35.9 kg: 250 mg>36.0 kg: 500 mg	3 d a week

IV, intravenous.

Prognosis

•Few outcome data exist in children.

•Some patients, especially those with postinfectious bronchiolitis obliterans, may have stable lung function for years.

•Other patients may have progressive disease despite therapy.

•Once fibrosis has set in, reversal of the disease may be challenging.

•There may be a role for antifibrotic therapy in this population.

When to Refer

•Establishing the correct diagnosis

•Treatment induction and maintenance therapy

•Disease follow-up and management of exacerbations

Resource for Families

•What Is Interstitial Lung Disease in Children? (American Thoracic Society) www.thoracic.org/patients/patient-resources/resources/interstitial-lung-disease-in-children.pdf

Clinical Pearls

•Consider a diagnosis of obliterative bronchiolitis in patients who have new shortness of breath, exercise intolerance, and/or crackles after a hematopoietic stem cell transplant or lung transplant.

•A diagnosis of obliterative bronchiolitis should also be considered in patients with a history of severe pneumonia, particularly with adenovirus, Stevens-Johnson syndrome, or measles, and poorly reversible airway obstruction (“atypical asthma”).

Part IV Bibliography

CHAPTER 45: UPPER RESPIRATORY INFECTIONS

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CHAPTER 46: LARYNGITIS

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CHAPTER 47: EPIGLOTTITIS

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CHAPTER 48: CROUP

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CHAPTER 49: PAPILLOMATOSIS

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CHAPTER 50: PERTUSSIS

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CHAPTER 51: BACTERIAL TRACHEITIS

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CHAPTER 52: BRONCHITIS

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CHAPTER 53: BRONCHIOLITIS

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CHAPTER 54: BACTERIAL PNEUMONIA

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•Jain S, Williams DJ, Arnold SR, et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015; 372(9):835–845

•Wilson S, Grundy R, Vyas H. Investigation and management of a child who is immunocompromised and neutropoenic with pulmonary infiltrates. Arch Dis Child Educ Pract Ed. 2009;94(5):129–137

CHAPTER 55: VIRAL PNEUMONIA

•Bradley JS, Byington CL, Shah SS, et al; Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):617–630

•Jain S, Williams DJ, Arnold SR, et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015; 372(9):835–845

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CHAPTER 56: MYCOPLASMA PNEUMONIA

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•Jain S, Williams DJ, Arnold SR, et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015; 372(9):835–845

•Biondi E, McCulloh R, Alverson B, Klein A, Dixon A, Ralston S. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014;133(6):1081–1090

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CHAPTER 57: CHLAMYDIAL PNEUMONIA

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•American Academy of Pediatrics Committee on Infectious Diseases. Chlamydial infections. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:284–294

CHAPTER 58: TUBERCULOSIS

•American Academy of Pediatrics. Tuberculosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:805–831

•Schmit KM, Wansaula Z, Pratt R, Price SF, Langer AJ. Tuberculosis—United States, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(11):289–294

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•World Health Organization. Global Tuberculosis Report 2014. http://www.who.int/tb/publications/global_report/en/. Accessed October 2, 2017

•Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/ Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017;64(2):e1–e33

CHAPTER 59: NONTUBERCULOUS MYCOBACTERIAL PULMONARY DISEASE

•Martiniano SL, Nick JA. Nontuberculous mycobacterial infections in cystic fibrosis. Clin Chest Med. 2015;36(1):101–115

•Griffith DE, Aksamit T, Brown-Elliott BA, et al; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175(4):367–416 y American Academy of Pediatrics Committee on Infectious Diseases. Diseases caused by nontuberculous mycobacteria. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:831–839

•Floto RA, Olivier KN, Saiman L, et al; US Cystic Fibrosis Foundation and European Cystic Fibrosis Society. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016;71(Suppl 1):i1–i22

CHAPTER 60: FUNGAL PNEUMONIA

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•Nania JJ, Wright PF. The mycoses. In: Wilmott RW, Boat TF, Bush A, Chernick V, Deterding RR, Ratjen F, eds. Kendig and Chernick’s Disorders of the Respiratory Tract in Children. Philadelphia, PA: Elsevier; 2012:531–544

•Wilson S, Grundy R, Vyas H. Investigation and management of a child who is immunocompromised and neutropoenic with pulmonary infiltrates. Arch Dis Child Educ Pract Ed. 2009;94(5):129–137

•Ostrosky-Zeichner L. Invasive mycoses: diagnostic challenges. Am J Med. 2012; 125(1 Suppl):S14–S24

•Patterson TF, Thompson GB III, Denning DW, et al. Practice guidelines for the diagnosis and management of Aspergillus: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63:e1–e60

CHAPTER 61: HISTOPLASMOSIS AND OTHER ENDEMIC FUNGAL PNEUMONIAS

•Hage CA, Azar MM, Bahr N, Loyd J, Wheat LJ. Histoplasmosis: up-to-date evidence-based approach to diagnosis and management. Semin Respir Crit Care Med. 2015;36(5):729–745

•Lease ED, Alexander BD. Fungal diagnostics in pneumonia. Semin Respir Crit Care Med. 2011;32(6):663–672

•Thompson GR III, Cadena J, Patterson TF. Overview of antifungal agents. Clin Chest Med. 2009;30:203–215

•Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112–e146

CHAPTER 62: COMPLICATIONS OF PNEUMONIA: PLEURAL EFFUSIONS

•Hendaus MA, Janahi IA. Parapneumonic effusion in children: an up-to-date review. Clin Pediatr (Phila). 2016;55(1):10–18

•Corcoran JP, Wrightson JM, Belcher E, DeCamp MM, Feller-Kopman D, Rahman NM. Pleural infection: past, present, and future directions. Lancet Respir Med. 2015;3(7):563–577

•Dorman RM, Vali K, Rothstein DH. Trends in treatment of infectious parapneumonic effusions in U.S. children’s hospitals, 2004-2014. J Pediatr Surg . 2016;51(6):885–890 y Mong A, Epelman M, Darge K. Ultrasound of the pediatric chest. Pediatr Radiol. 2012;42(11):1287–1297

•Kontouli K, Hatziagorou E, Kyrvasilis F, Roilides E, Emporiadou M, Tsanakas J. Long-term outcome of parapneumonic effusions in children: Lung function and exercise tolerance. Pediatr Pulmonol. 2015;50(6):615–620

CHAPTER 63: COMPLICATIONS OF PNEUMONIA: EMPYEMA

•Corcoran JP, Wrightson JM, Belcher E, DeCamp MM, Feller-Kopman D, Rahman NM. Pleural infection: past, present, and future directions. Lancet Respir Med. 2015;3(7):563–577

•Hendaus MA, Janahi IA. Parapneumonic effusion in children: an up-to-date review. Clin Pediatr (Phila). 2016;55(1):10–18

•Walker W, Wheeler R, Legg J. Update on the causes, investigation and management of empyema in childhood. Arch Dis Child. 2011;96(5):482–488

•Li S-TT, Tancredi DJ. Empyema hospitalizations increased in US children despite pneumococcal conjugate vaccine. Pediatrics. 2010;125(1):26–33

•Marhuenda C, Barceló C, Fuentes I, et al. Urokinase versus VATS for treatment of empyema: a randomized multicenter clinical trial. Pediatrics. 2014;134(5): e1301–e1307

•Stockmann C, Ampofo K, Pavia AT, et al. Comparative effectiveness of oral versus outpatient parenteral antibiotic therapy for empyema. Hosp Pediatr. 2015;5(12): 605–612

•Shah SS, Srivastava R, Wu S, et al; Pediatric Research in Inpatient Settings Network. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692

CHAPTER 64: COMPLICATIONS OF PNEUMONIA: PULMONARY ABSCESS

•Desai H, Agrawal A. Pulmonary emergencies: pneumonia, acute respiratory distress syndrome, lung abscess, and empyema. Med Clin North Am. 2012;96(6):1127–1148

•Bartlett JG. How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy. Infect Dis Clin North Am. 2013; 27(1):149–155

•Brook I. Anaerobic pulmonary infections in children. Pediatr Emerg Care. 2004;20(9): 636–640

CHAPTER 65: COMPLICATIONS OF PNEUMONIA: POSTINFECTIVE BRONCHIOLITIS OBLITERANS

•Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. N Engl J Med. 2014;370(19):1820–1828

•Welsh CH, Wang TS, Lyu DM, et al; The American Thoracic Society Implementation Task Force. An international ISHLT/ATS/ERS clinical practice guideline: summary for clinicians. Bronchiolitis obliterans syndrome complicating lung transplantation. Ann Am Thorac Soc. 2015;12(1):118–119

•Williams KM, Cheng GS, Pusic I, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(4):710–716

•Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr. 2008;20(3):272–278

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