ATS Reading List

Interstitial Lung Disease


An Official American Thoracic Society/European Respiratory Society Statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188:744-748. Written to standardize and update the diagnostic criteria and terminology for idiopathic interstitial pneumonias, this article nicely summarizes the clinical, radiologic, and histologic features of the ILD alphabet soup. Discusses recently described rare entities.
PMID: 24032382
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Meyer KC, Raghu G, Baughman RP, et al. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 2012;185:1004-14. This article offers some help in selecting patients most suitable for bronchoalveolar lavage. Arguably the greatest strength of the guideline is how it nicely pulls together clinical presentation and typical BAL findings for a wide spectrum of interstitial lung diseases, which is difficult to find assembled in one place.
PMID: 22550210

Larsen BT, Smith ML, Elicker BM, et al. Diagnostic approach to advanced fibrotic interstitial lung disease: bringing together clinical, radiologic, and histologic clues. Arch Pathol Lab Med. Epub 2016 Sep 15. doi: 10.5858/arpa.2016-0299-SA. A multidisciplinary review that provides overview of how to differentiate IPF from other progressive fibrotic lung disease such as chronic hypersensitivity pneumonitis and connective tissue disease-associated ILD.
PMID: 27628326
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Idiopathic Pulmonary Fibrosis

Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005;142:963-7. This retrospective study of 168 patients with mild to moderate disease from the placebo arm of the IFN-gamma 1b study found minimal change in physiologic variables among survivors during the 72 weeks of follow-up. 19% of patients died of IPF-related causes, of whom 47% experienced rapid clinical deterioration. These results indicate IPF exacerbations in patients with milder disease are not uncommon, which has implications for listing for lung transplantation.
PMID: 15968010

Flaherty KR, King TE, Raghu G et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004;170:904-10. This study found radiologists and clinicians with expertise in ILD reliably diagnose IPF without a lung biopsy when the clinical and imaging features are typical of IPF. Combining clinical, radiographic, and pathologic information heavily influenced the final diagnostic impression in non-IPF cases. Histology results had the greatest influence in these instances, but pathologists altered or clarified their diagnosis 19% of the time after receiving radiographic and clinical information.
PMID: 15256390

IPF Treatment

The following studies of pirfenidone and nintedanib are the first to clearly establish treatment benefit and have immediately become the standard of care for patients with mild to moderate disease. Whether patients with severe IPF or usual interstitial pneumonia pathology associated with collagen vascular disease will also benefit remains to be seen.

King TE, Jr., Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083-92. Year-long RCT of 555 patients with FVC 50 – 90% and DLCO 30 – 90% found pirfenidone slowed the rate of decline in FVC (23% vs. 9.7% placebo for no decline in FVC; 17% vs. 32% placebo for > 10% decline). Pirfenidone also improved the decline in 6-minute walk distance.
PMID: 24836312
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Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370:2071-82. Year-long RCT of 515 patients with FVC > 50% and DLCO 30 – 79% found nintedanib slowed the rate of decline in FVC (- 115 ml vs – 240 ml for placebo over 1 year). Over 60% of nintedanib subjects experienced diarrhea vs. 19% in placebo group but < 5% discontinued study drug.
PMID: 24836310
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Wijsenbeek MS, Culver DA. Treatment of sarcoidosis. Clin Chest Med. 2015;36:751-67. A review addressing a number of questions related to the treatment of sarcoidosis, including when to initiate treatment, treatment strategies, and the use of collaborative decision making.
PMID: 26593147

Cryptogenic Organizing Pneumonia

Lazor R, Vandevenne A, Pelletier A, et al. Cryptogenic organizing pneumonia: characteristics of relapses in a series of 48 patients. Am J Respir Crit Care Med 2000; 162:571-7. This retrospective case series provides insight on the clinical course of COP and has had a large influence on the way corticosteroids are used to treat COP.
PMID: 10934089


Tashkin DP, Elashoff R, Clements PJ, et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med 2007; 76:1026-1034. A prior study in this population found a year-long course of oral cyclophosphamide modestly improved FVC (2.5%), dyspnea, and quality of life compared to placebo.  This follow-up study assessed whether the benefits were sustained following treatment and found no difference at 12 months. Benefit was greatest in patients with a greater burden of fibrotic disease. These results provide a rationale for subsequent consolidation therapy with a less toxic agent if cyclophosphamide is used for initial treatment.
PMID: 17717203


Travis WD, Hunninghake G, King TE, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med; 2008; 177:1338-47. Based on review by a panel of experts, idiopathic NSIP does exist as a distinct clinical entity. However, diagnosis appears challenging, as only 67 of 193 previously reported cases of NSIP were determined to have NSIP by the panel using a combination of clinical, radiologic, pathologic assessment.
PMID: 18388353

Last Reviewed: June 2017