title: 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 SSc-related 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK, and University Hospital of Heraklion, Crete, Greece.
authors.forename: K M
authors.initials: KM
authors.lastname: Antoniou
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK, and University Hospital of Heraklion, Crete, Greece.
authors.forename: G A
authors.initials: GA
authors.lastname: Margaritopoulos
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Goh
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Karagiannis
authors.affiliation: King's College Hospital, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Desai
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust and National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Nicholson
authors.affiliation: University Hospital of Heraklion, Crete, Greece.
authors.forename: N M
authors.initials: NM
authors.lastname: Siafakas
authors.affiliation: Royal Free Hospital and University College London Medical School, London, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Coghlan
authors.affiliation: Royal Free Hospital and University College London Medical School, London, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Hansell
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, London, UK.
authors.forename: A U
authors.initials: AU
authors.lastname: Wells
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D004452:Echocardiography; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000209:etiology; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015995:Prevalence; D011653:Pulmonary Diffusing Capacity; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000150:complications / Q000453:epidemiology* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity