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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11790668

Mathieson JR, Mayo JR, Staples CA, Muller NL. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and chest radiography. Radiology 1989;171:111-6. First study to assess accuracy of CT-based diagnosis for patients with ILD. Correctly diagnosed UIP in 89% of cases, sarcoid in 77% of cases, and were, for the most part, less accurate in diagnosing less common diseases. Includes an interesting table of the frequency of selected CT findings observed among the 5 most common ILDs in the study (e.g. pleural fluid/thickening seen in only 9% of UIP cases). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2928513

 
BOOP/COP

Epler GR, Colby TV, McCloud TC, et al. Bronchiolitis obliterans organizing pneumonia. New Engl J Med 1985;312:152-8. Classic article describing idiopathic BOOP (cryptogenic organizing pneumonia) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3965933

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. http://www.ncbi.nlm.nih.gov/pubmed/10934089?ordinalpos=18&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 
Idiopathic Pulmonary Fibrosis

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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16306520&query_hl=6&itool=pubmed_docsum  
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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=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. 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15256390

Raghu G, Brown KK, Bradford WZ et al . A placebo controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004;350:125-33. A RCT of Gamma-1b IFN involving 330 patients found no difference in progression-free survival, pulmonary function, or quality of life in patients with IPF unresponsive to corticosteroid therapy.  A trend towards enhanced survival in adherent patients with less severe lung impairment (FVC >62 % predicted) prompted the INSPIRE trial which is in progress. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14711911

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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=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. http://www.ncbi.nlm.nih.gov/pubmed/15189938?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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. http://www.ncbi.nlm.nih.gov/pubmed/18539243?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

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. http://www.ncbi.nlm.nih.gov/pubmed/16790698?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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.  http://www.ncbi.nlm.nih.gov/pubmed/17717203?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

**See also Pulmonary Hypertension, Lung Transplantation, and Occupational Medicine