Interstitial Lung Disease

Overviews

American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277-304. Written to standardize the diagnostic criteria and terminology for idiopathic interstitial pneumonias, this article nicely summarizes the clinical, radiologic, and histologic features of the ILD alphabet soup.
PMID: 11790668
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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. 58% of patients experienced a relapse, 82% of which occurred within 1 year of the initial episode. Two-thirds of patients were on corticosteroids at the time of first relapse; only 1 patient was on > 20 mg/day of prednisone. Delayed treatment was a risk factor for relapse. Relapses did not affect longer term outcome.
PMID: 10934089
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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
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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
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Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of IPF. Am Rev Respir Dis 1991;144:291-6. RCT of prednisone plus azathioprine vs. prednisone alone found some patients had greater benefit with the combination of drugs, but overall differences between groups did not reach statistical significance. Some current trials of new therapies use this combination as the “standard therapy” control group.
PMID: 1859050

Collard HR, Ryu JH, Douglas WW, et al. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest. 2004; 125:2169-74. Retrospective analysis found no benefit in 82 treated vs. 82 untreated patients matched for age and FVC.
PMID: 15189938
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Taniguchi T, Ebina M, Kondoh Y, et al. Pirfenidone clinical study group in Japan. pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J 2010; 35: 821-9. The recent decision by the FDA not to approve pirfenidone has proven to be controversial. This multicenter, double-blind placebo-controlled phase III clinical trial of oral pirfenidone in IPF. Results demonstrated a statistically significant reduction in rate of decline in vital capacity (-0.09 L vs -0.16 L) as well as improvement in progression-free survival in patients treated with pirfenidone. Issues with study design raise caution in interpretation of the results. Two additional clinical studies are now completed and under review.
PMID: 19996196
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Demedts M, Behr J, Buhl R, et al, IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005; 353:2229-42. Multi-center, double-blind, randomized, placebo-controlled study (N=182) which determined (after one year) that high-dose oral acetylcysteine added to standard therapy (prednisone and azathioprine) resulted in modest benefit in terms of preserving vital capacity and DLCO but offered no survival advantage. A large proportion of patients dropped out of the study and there is concern that acetylcysteine prevented azathioprine toxicity rather than treated IPF.
PMID: 16306520
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Sarcoidosis

Baughman RP, Costabel U, du Bois RM. Treatment of sarcoidosis. Clin Chest Med 2008; 29:533-48. Offers some additional information since the 1999 ATS/ERS statement on sarcoidosis. Additional articles in this issue of Clin Chest Med cover other aspects of sarcoidosis.
PMID: 18539243

Scleroderma

Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006; 354:2655-66. Multi-center, double-blind, randomized, placebo-controlled trial of 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammation based on BAL fluid, thoracic high-resolution computed tomography, or both. One year of oral cyclophosphamide had a modest improvement in FVC (2.5%, p < .03), dyspnea, thickening of the skin, and quality of life. The effects on lung function were maintained through the 24 months of the study.
PMID: 16790698
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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;176:1026-1034. This follow-up study to the one cited above found the benefits of cyclophosphamide treatment extended to 6, but not 12, months after completion of treatment. 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 such as mycophenolate mofetil.
PMID: 17717203
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NSIP

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
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