Combined Pulmonary Fibrosis and Emphysema in Scleroderma‐Related Lung Disease Has a Major Confounding Effect on Lung Physiology and Screening for Pulmonary Hypertension

Abstract

Objective. To assess the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD) and the effect of CPFE on the pulmonary function tests used to evaluate the severity of SSc-related ILD and the likelihood of pulmonary hypertension (PH).Methods. High-resolution computed tomography (HRCT) scans were obtained in 333 patients with SScrelated ILD and were evaluated for the presence of emphysema and the extent of ILD. The effects of emphysema on the associations between pulmonary function variables and the extent of SSc-related ILD as visualized on HRCT and echocardiographic evidence of PH were quantified.Results. Emphysema was present in 41 (12.3%) of the 333 patients with SSc-related ILD, in 26 (19.7%) of 132 smokers, and in 15 (7.5%) of 201 lifelong nonsmokers. When the extent of fibrosis was taken into account, emphysema was associated with significant additional differences from the expected values for diffusing capacity for carbon monoxide (DLCO) (average reduction of 24.1%; P < 0.0005), and the forced vital capacity (FVC)/DLCO ratio (average increase of 34.8%; P < 0.0005) but not FVC. These effects were identical in smokers and nonsmokers. Multivariate analysis showed that the presence of emphysema had a greater effect than echocardiographically determined PH on the FVC/DLCO ratio, regardless of whether it was analyzed as a continuous variable or using a threshold value of 1.6 or 2.0.Conclusion. Among patients with SSc-related ILD, emphysema is sporadically present in nonsmokers and is associated with a low pack-year history in smokers. The confounding effect of CPFE on measures of gas exchange has major implications for the construction of screening algorithms for PH in patients with SSc-related ILD.Pulmonary involvement (including interstitial lung disease [ILD] and pulmonary hypertension [PH]) is the most common cause of death among patients with

Pulmonary hypertension in systemic sclerosis: different phenotypes

“…This syndrome is characterised by the association of severe dyspnoea, paraseptal emphysema and diffuse infiltrative opacities suggestive of pulmonary fibrosis, occurring most often in smokers [23]. As a consequence spirometry is usually normal, contrasting with very severely impaired DLCO and hypoxaemia during exercise (with a major confounding effect on the forced vital capacity/DLCO ratio [24]). Interestingly, this syndrome is associated with a high risk of PH, as identified in more than 50% of patients [23,25].…”

“…As lung volumes can be normal, it is possible that this syndrome is underdiagnosed in SSc. Recently, ANTONIOU et al [24] showed that emphysema in patients with SSc-related ILD can also be observed in nonsmokers and smokers with a low pack-year history. The significant prevalence of emphysema in nonsmokers with SSc-related ILD provides indirect support for a pathogenetic basis for the CPFE syndrome.…”

Comorbidities in interstitial lung diseases

“…In SSc, an elevated FVC/DLCO ratio (in essence, the inverse of KCO) was found to be an independent predictor for the presence of PH and is included in the DETECT as an indication for the performance of echocardiography [65]. However, in SSc patients with combined pulmonary fibrosis and emphysema (CPFE), elevation of FVC/DLCO is usual, irrespective of the presence or absence of pulmonary vasculopathy [66]. Use of FVC/DLCO has also been explored in IPF but this variable suffers from measurement variability as three variables must be measured (FVC, KCO and VA) whereas KCO is quantified as a single variable (integrated with VA in the computation of DLCO).…”

Major lung complications of systemic sclerosis

“…When considering lung function tests, it is important to consider that concurrent emphysema might reduce the utility of measuring gas exchange (DLCO) in patients for screening as it may increase FVC and diminish DLco independent of pulmonary hypertension. [78,79]. The DETECT cohort included patients with mild PAH and specific determinants of PAH progression have been elucidated using data from this cohort [80] and align with variables such as Nt-pro-BNP and low DLco identified in other cohorts [52,81,82].…”