Pulmonary hypertension (PHT) is an important complication of systemic sclerosis (SSc). Echocardiography can be used to detect PHT and, with Doppler echocardiography, the pulmonary arterial systolic pressure (PASP) can often be estimated. We have undertaken a study to compare echocardiographic assessment with right heart catheterization (RHC) in 33 SSc patients in whom clinical assessment [including ECG, chest X-ray, lung function tests and high-resolution computed tomography (HRCT) had raised strong suspicion of PHT. The mean (S.D.) interval between echocardiography and RHC was 1.8 (2.3) months. Twenty-one patients (64%) had PHT (PASP > or = 30 mmHg) on RHC, and echocardiography correctly identified 19 of these (sensitivity 90%). Of the 12 patients without PHT on RHC, nine were correctly identified by echocardiography (specificity 75%). The five incorrectly classified patients all had PASP in the borderline normal/abnormal range. The presence of tricuspid regurgitation allowed Doppler measurement of PASP in 20 patients (61%) and this correlated significantly with RHC values (r = 0.83, P < 0.001). We conclude that echocardiography is a reliable method for detecting PHT and it may be particularly useful for the early detection and monitoring of this potentially fatal complication in SSc.

In most clinical series of patients with cryptogenic fibrosing alveolitis (CFA), disease severity is staged using lung function indices. However, many physiologic indices are measured in routine clinical practice; the choice of variable to evaluate functional severity is contentious. Computed tomography (CT) provides a reproducible means of quantifying the morphologic extent of disease. The aim of this study was to evaluate the functional consequences of smoking-related lung damage in CFA and to identify functional measures best reflecting the extent of fibrosing alveolitis on CT. Sixty-eight patients with CFA were studied. Fourteen patients with emphysema on CT were characterized by relative preservation of FVC and TLC (p < 0.005) and relative depression of DLCO (p < 0.05) and KCO (p < 0.00005). On multivariate analysis, the extent of fibrosing alveolitis and the presence of emphysema were independent determinants of functional impairment; there was no independent relationship between smoking history and functional abnormalities. In patients without emphysema on CT, percent predicted DLCO (r = -0.68), oxygen desaturation on exercise (r = 0.64), and the physiologic component of the clinical-radiographic-physiologic (CRP) score (r = 0.62) correlated much better with the extent of disease on CT than spirometric and plethysmographic volumes. A composite functional index was generated against the extent of disease on CT, using multivariate analysis; comparison with the CRP score suggested that the relationship between morphologic disease extent and the CRP score would be improved by the inclusion of DLCO and by the use of negative weighting for depression of FEV1. These findings indicate that in CFA, the presence of concurrent emphysema on CT has a more profound influence upon functional measures than the smoking history, and underline the importance of both the measurements of DLCO and exercise testing in the assessment of the severity of CFA.

There are significant differences in the extent of interstitial fibrosis, lymphoid follicles and eosinophilic infiltration between DIP and RB, as well as a much lower incidence of smoking in patients with DIP. Whether the lower reported incidence of smoking in DIP reflects referral bias or conservatism in giving a history of smoking remains uncertain, as neither histological parameters nor clinical data indicate a difference between smokers and never-smokers with DIP. Nevertheless, some cases of DIP are likely to remain idiopathic and unrelated to RB, though still have a good prognosis. Furthermore, they may evolve into a pattern resembling fibrotic NSIP. Therefore, whilst SR-ILD is appropriate in the correct clinical setting, the distinction between the histological patterns of RB and DIP remains appropriate.

Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in ∼3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DPβ-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DPβ69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DPβ Glu69 in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-γ (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.

Abstract. du Bois RM,