Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.

BACKGROUND: Desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are uncommon forms of interstitial lung disease and have been incompletely characterized. STUDY OBJECTIVES: To further characterize the clinical features and course of subjects with DIP and RB-ILD. DESIGN: Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS: Twenty-three subjects with DIP and 12 subjects with RB-ILD seen over a 12-year period between 1990 and 2001. INTERVENTIONS: None. RESULTS: The study population included 19 men (54%) and 16 women (46%). The mean (+/- SD) age at diagnosis was 46 +/- 10 and 43 +/- 7 years, respectively, for patients with DIP and RB-ILD. All subjects were either current or previous smokers except for three subjects with DIP. The diagnosis was confirmed in all cases by surgical lung biopsy. Bronchoscopy with transbronchial lung biopsy had been performed in 12 patients and was nondiagnostic in all. The most common pulmonary function abnormality was a reduced diffusing capacity of the lung for carbon monoxide. A CT scan of the chest revealed ground-glass opacities bilaterally in most patients who had DIP and RB-ILD. No differences were observed between subjects with DIP and RB-ILD with respect to clinical features, radiologic findings, or pulmonary function test results. The clinical course was characterized by relative stability in the majority of patients in both groups and a partial response to corticosteroid therapy. Five deaths were observed, including three resulting from progressive diffuse lung disease, all in subjects with DIP. CONCLUSIONS: We concluded that DIP and RB-ILD are chronic disease processes that in most patients are related to smoking. Persistent abnormalities can be seen on pulmonary function testing and radiologic studies despite smoking cessation and corticosteroid therapy. Corticosteroid therapy appeared to be associated with modest clinical benefit but usually not with resolution of disease. Progressive disease with eventual death can occur in subjects with DIP, especially with continued cigarette smoking.

Primary pulmonary carcinoma in patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To identify distinguishing characteristics between patients with idiopathic pulmonary fibrosis (IPF) and primary lung carcinoma and patients with either IPF or carcinoma alone. PATIENTS AND METHODS: The study group consisted of 24 patients with histologically proven usual interstitial pneumonia and lung carcinoma identified through a search of the Rochester Mayo Clinic database for 1990 to 1998. Medical records, radiographs, and histological slides were reviewed. Several variables including survival were compared in 2 control groups, IPF only and carcinoma only, by using various statistical methods. RESULTS: Our study group included 21 men and 3 women (mean age, 72.3 years). Twenty-two were past or current smokers. Approximately half of the lung carcinomas were incidental findings. Of the 14 patients with preoperative computed tomographic scans, 12 had peripheral tumors situated in areas of fibrosis. Squamous cell carcinoma was the most common histological type, accounting for 16 cases. Almost all patients underwent surgical treatment; nearly 40% developed postoperative complications, and 3 died within 30 days of surgery. The ratio of men to women in patients with IPF and carcinoma was 7:1 compared with 1:1 in patients with IPF only (P=.003). Patients with IPF and carcinoma were also older, with a mean age of 72.3 years compared with 64.4 years (P=.001), and were more often smokers (P=.002). Carcinomas involved the lower lobes in 42% of patients with IPF and carcinoma compared with 29% of patients with carcinoma only (P=.004) and were mainly composed of squamous cell carcinoma (P=.004). Mean survival in patients with IPF and lung carcinoma was 2.3 years after the diagnosis of IPF and 1.6 years after that of carcinoma. This finding did not differ significantly from survival of patients with either IPF or carcinoma alone. However, statistical power was limited. CONCLUSION: Carcinoma in patients with IPF arises in older male smokers and usually presents as peripheral squamous cell carcinoma. The prognosis is poor.

Impact of angiotensin-converting enzyme inhibitors and statins on survival in idiopathic pulmonary fibrosis.

STUDY OBJECTIVES: To assess the clinical relevance of angiotensin-converting enzyme inhibitors (ACEI) and 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) in the context of idiopathic pulmonary fibrosis (IPF). BACKGROUND: IPF is a progressive interstitial lung disease for which there is no effective treatment. ACEI and statins have been shown to possess antifibrotic properties in experimental models in vitro and in vivo. DESIGN, SETTING, AND PATIENTS: Retrospective review of the effects of ACEI and statins on survival of 478 patients with IPF seen at Mayo Clinic Rochester from 1994 through 1996. Fifty-two patients (11%) were receiving ACEI, 35 patients (7%) were receiving statins, and 5 patients (1%) patients were receiving both at their initial visit. RESULTS: For subjects receiving ACEI, the median survival from the index visit was 2.2 years, compared to 2.9 years for subjects not receiving ACEI (p = 0.088). The median survival was 2.9 years if patients were receiving statins or not (p = 0.573). There was also no significant difference in survival between patients with IPF receiving either ACEI or statins vs those receiving neither at the index visit (2.5 years vs 3 years, respectively; p = 0.066). After adjusting for age, gender, recommended IPF treatment, smoking status, prior oxygen use, FVC, diffusion capacity for carbon monoxide, coronary artery disease, congestive heart failure, diabetes mellitus, and hypertension, there were no differences in survival between those subjects receiving either ACEI, statins, or both vs neither. CONCLUSIONS: These data do not suggest a beneficial effect of ACEI and/or statins on survival in patients with IPF.

The overlap between respiratory bronchiolitis and desquamative interstitial pneumonia in pulmonary Langerhans cell histiocytosis: high-resolution CT, histologic, and functional correlations.

OBJECTIVES: To characterize the histologic, high-resolution CT (HRCT), and functional correlates of respiratory bronchiolitis (RB)/desquamative interstitial pneumonia (DIP)-like changes in biopsy specimens of adults with pulmonary Langerhans cell histiocytosis (PLCH). METHODS: We retrospectively identified 14 adult patients with histologically proven PLCH (all smokers) in whom both biopsy specimens and HRCT were available for review. The presence and extent of RB/DIP-like changes on lung biopsy specimens of patients with PLCH were correlated with total pack-years of smoking, lung function variables, and the presence of ground-glass attenuation on HRCT. RESULTS: Varying degrees of RB/DIP-like changes were identified in all biopsy specimens. The extent of involvement with RB/DIP-like changes correlated with the cumulative exposure to cigarettes smoked at the time of biopsy (r = 0.61, p = 0.03). Ground-glass attenuation was detected in three HRCTs, two of which had extensive RB/DIP-like changes (> or = 70% involvement) on histology, suggesting that substantial smoking-induced RB/DIP-like changes may be the cause of ground-glass attenuation on the HRCT of patients with PLCH. No correlation was found between the extent of RB/DIP-like changes and total lung capacity, FEV(1), or diffusion capacity of the lung for carbon monoxide. CONCLUSIONS: RB/DIP-like changes are exceedingly common in PLCH, may be sufficiently severe to cause the appearance of ground-glass attenuation on HRCT, and correlate with the cumulative exposure to cigarettes smoked. This study provides additional evidence that PLCH, RB, and DIP form a spectrum of interstitial patterns of lung injury to cigarette smoke.

Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis.

STUDY OBJECTIVES: Treatment of patients with idiopathic pulmonary fibrosis (IPF) conventionally includes corticosteroids and cytotoxic agents. No study to date has adequately evaluated the benefits of this approach. This study retrospectively compared combination corticosteroid and cyclophosphamide therapy in a large population of patients who meet the current consensus definition of IPF. DESIGN: Patients were identified retrospectively and treatment addressed on an intention-to-treat basis. Treated and untreated patients were matched by age and percentage of predicted FVC (FVC%) at the time of the initial visit. SETTING: Two academic tertiary referral centers. PATIENTS OR PARTICIPANTS: The diagnosis of IPF was based on current consensus criteria. A total of 164 patients (82 treated and 82 untreated) were included. INTERVENTIONS: Treatment consisted of combined corticosteroid and cyclophosphamide therapy using a standardized protocol. MEASUREMENTS AND RESULTS: There was no difference in age, FVC%, gender, or smoking status between groups. No survival difference was found between patients who were treated (median survival, 1,431 days) or untreated (median survival, 1,665 days) [p = 0.58]. The lack of treatment effect persisted when only those patients with a diagnosis by surgical biopsy (n = 24) or FVC% >/= 60 (n = 107) were analyzed. CONCLUSIONS: Our data suggest that combined corticosteroid and cyclophosphamide therapy has no impact on survival in patients with IPF. This finding supports the evolving concept that chronic inflammation plays a minimal role in the progression of IPF and reinforces the importance of careful consideration of the risks and benefits of such therapies prior to their institution.