Respiratory bronchiolitis-associated interstitial lung disease
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a type of idiopathic interstitial pneumonia (IIP) that has pathologic features of respiratory bronchiolitis (RB). The other IIPs include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), lymphocytic interstitial pneumonia (LIP), and cryptogenic organizing pneumonia (COP).
The clinical presentation, diagnosis, treatment, and prognosis of RB-ILD will be reviewed here. The evaluation and diagnosis of interstitial lung disease, including the idiopathic interstitial pneumonias, and bronchiolitis are discussed separately. (See "Idiopathic interstitial pneumonias: Clinical manifestations and pathology" and "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Treatment and prognosis of nonspecific interstitial pneumonia" and "Acute interstitial pneumonia (Hamman-Rich syndrome)" and "Lymphoid interstitial pneumonia in adults" and "Cryptogenic organizing pneumonia" and "Bronchiolitis in adults".)
Respiratory (or "smoker's") bronchiolitis (RB) is a well-recognized pathological lesion found in the lungs of many cigarette smokers that is generally not associated with respiratory symptoms. The key features of RB are the pathologic findings of tan-pigmented macrophages (also known as smokers' macrophages) in the respiratory bronchioles, a patchy submucosal and peribronchiolar infiltrate of lymphocytes and histiocytes, and peribronchiolar fibrosis that extends into contiguous alveolar walls. (See 'Histopathology' below.)
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is defined by the presence of changes of RB as the sole pathologic finding in a current or former cigarette smoker with clinical evidence of interstitial lung disease [1-7]. The degree to which fibrosis extends into the alveolar wall has sometimes been used to distinguish RB from RB-ILD, but most pathologists believe that the two processes cannot be distinguished on pathologic grounds alone [1,8-11]. Thus, RB-ILD probably represents a subset of individuals with a more severe stage in the spectrum of RB and is much less common than RB.
RB is a common finding among smokers, but RB-ILD is uncommon. As an example, in a series of 79 smokers with spontaneous pneumothorax requiring surgical intervention, RB was found in 89 percent of the lung biopsies . Although the exact incidence of RB-ILD is not known, in a review of 168 lung biopsies performed for suspicion of idiopathic pulmonary fibrosis, 10 were RB-ILD . (See 'Histopathology' below and "Idiopathic interstitial pneumonias: Clinical manifestations and pathology".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Fraig M, Shreesha U, Savici D, Katzenstein AL. Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex-smokers, and never-smokers. Am J Surg Pathol 2002; 26:647.
- Craig PJ, Wells AU, Doffman S, et al. Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking. Histopathology 2004; 45:275.
- Wright JL, Lawson LM, Pare PD, et al. Morphology of peripheral airways in current smokers and ex-smokers. Am Rev Respir Dis 1983; 127:474.
- Myers JL, Veal CF Jr, Shin MS, Katzenstein AL. Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases. Am Rev Respir Dis 1987; 135:880.
- Guerry-Force ML, Müller NL, Wright JL, et al. A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial pneumonia, and small airways disease. Am Rev Respir Dis 1987; 135:705.
- Yousem SA, Colby TV, Gaensler EA. Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. Mayo Clin Proc 1989; 64:1373.
- King, TE Jr, Mortenson, RL. Syndromes that mimic idiopathic pulmonary fibrosis. Immunol Allergy Clin North Am 1992; 12:461.
- Niewoehner DE, Kleinerman J, Rice DB. Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med 1974; 291:755.
- Wells AU, Nicholson AG, Hansell DM. Challenges in pulmonary fibrosis . 4: smoking-induced diffuse interstitial lung diseases. Thorax 2007; 62:904.
- Churg A, Müller NL, Wright JL. Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. Arch Pathol Lab Med 2010; 134:27.
- Yousem SA. Respiratory bronchiolitis-associated interstitial lung disease with fibrosis is a lesion distinct from fibrotic nonspecific interstitial pneumonia: a proposal. Mod Pathol 2006; 19:1474.
- Cottin V, Streichenberger N, Gamondès JP, et al. Respiratory bronchiolitis in smokers with spontaneous pneumothorax. Eur Respir J 1998; 12:702.
- Moon J, du Bois RM, Colby TV, et al. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease. Thorax 1999; 54:1009.
- Carilli AD, Kotzen LM, Fischer MJ. The chest roentgenogram in smoking females. Am Rev Respir Dis 1973; 107:133.
- Weiss W. Cigarette smoke, asbestos, and small irregular opacities. Am Rev Respir Dis 1984; 130:293.
- Weiss W. Cigarette smoking and small irregular opacities. Br J Ind Med 1991; 48:841.
- Dick JA, Morgan WK, Muir DF, et al. The significance of irregular opacities on the chest roentgenogram. Chest 1992; 102:251.
- McWilliams AM, Lake FR. Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) presenting with haemoptysis. Respirology 2000; 5:385.
- Mavridou D, Laws D. Respiratory bronchiolitis associated interstitial lung disease (RB-ILD): a case of an acute presentation. Thorax 2004; 59:910.
- Sadikot RT, Johnson J, Loyd JE, Christman JW. Respiratory bronchiolitis associated with severe dyspnea, exertional hypoxemia, and clubbing. Chest 2000; 117:282.
- Ryu JH, Myers JL, Capizzi SA, et al. Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease. Chest 2005; 127:178.
- Bogin RM, Niccoli SA, Waldron JA, et al. Respiratory bronchiolitis: Clinical presentation and bronchoalveolar lavage findings. Chest 1988; 94:s21.
- Portnoy J, Veraldi KL, Schwarz MI, et al. Respiratory bronchiolitis-interstitial lung disease: long-term outcome. Chest 2007; 131:664.
- Park JS, Brown KK, Tuder RM, et al. Respiratory bronchiolitis-associated interstitial lung disease: radiologic features with clinical and pathologic correlation. J Comput Assist Tomogr 2002; 26:13.
- Lynch DA, Schwarz MI, Heinig MT, et al. Respiratory bronchiolitis: Radiographic assessment. Presented at Society of Thoracic Radiology, 1990.
- Heyneman LE, Ward S, Lynch DA, et al. Respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative interstitial pneumonia: different entities or part of the spectrum of the same disease process? AJR Am J Roentgenol 1999; 173:1617.
- Holt RM, Schmidt RA, Godwin JD, Raghu G. High resolution CT in respiratory bronchiolitis-associated interstitial lung disease. J Comput Assist Tomogr 1993; 17:46.
- Remy-Jardin M, Remy J, Gosselin B, et al. Lung parenchymal changes secondary to cigarette smoking: pathologic-CT correlations. Radiology 1993; 186:643.
- American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002; 165:277.
- Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 Suppl 5:v1.
- Cosio MG, Hale KA, Niewoehner DE. Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis 1980; 122:265.
- Colby TV. Bronchiolitis. Pathologic considerations. Am J Clin Pathol 1998; 109:101.
- Myers JL, Katzenstein AL. Beyond a consensus classification for idiopathic interstitial pneumonias: progress and controversies. Histopathology 2009; 54:90.
- Kawabata Y, Hoshi E, Murai K, et al. Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course. Histopathology 2008; 53:707.
- Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E. Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum Pathol 2010; 41:316.
- Reddy TL, Mayo J, Churg A. Respiratory bronchiolitis with fibrosis. High-resolution computed tomography findings and correlation with pathology. Ann Am Thorac Soc 2013; 10:590.
- English C, Churg A, Lam S, Bilawich AM. Respiratory bronchiolitis with fibrosis: prevalence and progression. Ann Am Thorac Soc 2014; 11:1665.
- Churg A, Hall R, Bilawich A. Respiratory bronchiolitis with fibrosis-interstitial lung disease: a new form of smoking-induced interstitial lung disease. Arch Pathol Lab Med 2015; 139:437.
- Churg A, Wright JL. Small airways disease and mineral dust exposure. Pathol Annu 1983; 18 Pt 2:233.
- Churg A, Wright JL. Small-airway lesions in patients exposed to nonasbestos mineral dusts. Hum Pathol 1983; 14:688.
- Davies G, Wells AU, du Bois RM. Respiratory bronchiolitis associated with interstitial lung disease and desquamative interstitial pneumonia. Clin Chest Med 2004; 25:717.
- Nakanishi M, Demura Y, Mizuno S, et al. Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation. Eur Respir J 2007; 29:453.
- O'Beirne S, Counihan IP, Keane MP. Interstitial lung disease and lung transplantation. Semin Respir Crit Care Med 2010; 31:139.
- Scheidl SJ, Kusej M, Flick H, et al. Clinical Manifestations of Respiratory Bronchiolitis as an Incidental Finding in Surgical Lung Biopsies: A Retrospective Analysis of a Large Austrian Registry. Respiration 2016; 91:26.
- CLINICAL FEATURES
- EVALUATION AND DIAGNOSIS
- Diagnostic criteria
- Laboratory studies
- Pulmonary function tests
- Surgical lung biopsy
- DIFFERENTIAL DIAGNOSIS
- Smoking cessation
- Supportive therapy
- Glucocorticoid and immunosuppressive therapy
- Lung transplantation
- SUMMARY AND RECOMMENDATIONS