Significance of connective tissue disease features in idiopathic interstitial pneumonia.

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.

Optimal scoring of serial change on chest radiography in sarcoidosis.

BACKGROUND: The optimal means of quantifying change on chest radiography in sarcoidosis is uncertain. In current guidelines, the role of serial measurement of carbon-monoxide diffusing capacity (DLco) remains undefined and the prevalence of discordance between serial chest radiographic change and pulmonary function tends is unknown. OBJECTIVE: To identify and explore key uncertainties in the monitoring of sarcoidosis by serial pulmonary function tests and chest radiography. DESIGN: 354 patients with sarcoidosis and concurrent tests (chest radiography and PFTs within three months at baseline, two years and/or four years) were studied. Chest radiographs were assessed by two radiologists for changes in stage and disease extent. Radiographic change and pulmonary function trends were quantified and compared. RESULTS: Change in radiographic extent of lung disease was always more frequent than change in stage (p < 0.0001) and there was poor agreement between change in stage and change in radiographic extent (Kw = 0.21 at two years; Kw = 0.23 at four years). Change in disease extent on chest radiography was linked to PFT trends on analysis of variance (p < 0.0005 for FEV1, FVC, DLco), whereas change in radiographic stage was not. Changes in gas transfer were often isolated or discordant with other serial data. Discordance between pulmonary function data and chest radiographic data was observed in 50% of cases. CONCLUSIONS: Change in radiographic extent is more applicable to routine monitoring in sarcoidosis than change in radiographic stage. In future guidelines, the role of serial gas transfer estimation and reconciliation of divergent chest radiographic and functional trends might usefully be addressed.

Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis.

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of "marginal" changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D( L,CO)) trends at 6 months were categorised as "significant" (FVC >10%; D(L,CO) >15%) or "marginal" (FVC 5-10%; D(L,CO) 7.5-15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality. In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54-5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19-4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19-4.60; p = 0.01). Marginal changes in D(L,CO) in IPF and marginal changes in FVC and D (L,CO) in fibrotic NSIP did not provide useful prognostic information. Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.