Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression (i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD (i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide (DLCO) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted DLCO Only five studies specifically aimed to validate the PFTs: two concluded that DLCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that DLCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression.

Caron M ，Hoa S ，Hudson M ，Schwartzman K ，Steele R ... -  《-》

Quantifying change in pulmonary function as a prognostic marker in systemic sclerosis-related interstitial lung disease.

Moore OA ，Proudman SM ，Goh N ，Corte TJ ，Rouse H ，Hennessy O ，Morrisroe K ，Thakkar V ，Sahhar J ，Roddy J ，Youssef P ，Gabbay E ，Nash P ，Zochling J ，Stevens W ，Nikpour M ... -  《CLINICAL AND EXPERIMENTAL RHEUMATOLOGY》

Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis.

Showalter K ，Hoffmann A ，Rouleau G ，Aaby D ，Lee J ，Richardson C ，Dematte J ，Agrawal R ，Chang RW ，Hinchcliff M ... -  《-》

Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis.

To determine the prognostic value of pulmonary function test (PFT) trends at 1 and 2 years in interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The prognostic significance of PFT trends at 1 year (n = 162) and 2 years (n = 140) was examined against 15-year survival in patients with SSc-associated ILD. PFT trends, expressed as continuous change and as categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-associated ILD was defined at presentation as either limited lung fibrosis or extensive lung fibrosis, using the United Kingdom Raynaud's and Scleroderma Association severity staging system. One-year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical change in the forced vital capacity (FVC), alone or in combination with categorical change in the diffusing capacity for carbon monoxide (DLco), had greater prognostic significance than continuous change in the FVC or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite end point, consisting of either an FVC decline from baseline of ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At 2 years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in those with limited lung fibrosis. However, in patients with extensive lung fibrosis, the above-defined FVC and DLco composite end point was the strongest prognostic determinant. Larger changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient were required to achieve prognostic significance. Based on linkages to long-term outcomes, these findings provide support for use of routine spirometry and gas transfer monitoring in patients with SSc-associated ILD, with further evaluation of a composite FVC and DLco end point warranted for trial purposes.

Goh NS ，Hoyles RK ，Denton CP ，Hansell DM ，Renzoni EA ，Maher TM ，Nicholson AG ，Wells AU ... -  《-》

Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease.

Validated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high-resolution computed tomography (HRCT) of the chest for the detection of SSc-related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT. Prospectively enrolled patients with SSc were assessed according to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research standards. The assessment included PFTs and HRCT. The HRCT images were evaluated in a blinded manner by 2 experienced radiologists. The performance parameters of PFTs for the diagnosis of SSc-related ILD were calculated. Predictors of significant ILD as determined by HRCT in patients with normal forced vital capacity (FVC) values were identified through logistic regression. Among the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while only 27 (26.0%) had an FVC <80% of predicted, and 54 (53.0%) had a decrease in the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD on HRCT had a normal FVC value, translating into a high false-negative rate. Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult lung fibrosis; in 2 of these patients, the results of all of the PFTs were within normal limits. Patients with normal FVC values despite evidence of fibrosis on HRCT more frequently had anti-Scl-70 antibodies and diffuse SSc and less frequently had anticentromere antibodies (ACAs) compared with patients with both normal FVC values and normal HRCT results. The derived evidence-based data reveal a high risk of missing significant SSc-related ILD when relying solely on PFTs. More comprehensive screening algorithms for early detection are warranted. In particular, additional imaging investigations for the early detection of SSc-related ILD should be considered in ACA-negative patients with normal FVC values.

Suliman YA ，Dobrota R ，Huscher D ，Nguyen-Kim TD ，Maurer B ，Jordan S ，Speich R ，Frauenfelder T ，Distler O ... -  《-》