FAM13A polymorphism is associated with a usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease.

The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis (RA)-related interstitial lung disease (ILD), but not with systemic sclerosis (SSc)-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general. We performed a cross-sectional study of SSc-ILD patients from 4 US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and non-UIP groups. Analysis of HRCTs performed by a thoracic radiologist blinded to participants' characteristics classified each scan as definite UIP, probable UIP, indeterminate, or alternative diagnosis, according to American Thoracic Society criteria. Four-hundred eighty-nine SSc-ILD patients were included; 80% were female and 75% were White. Twenty-three (4.7%) patients had a definite UIP pattern. The MUC5B SNP rs35705950 was not associated with a definite UIP pattern in SSc-ILD. In contrast, patients carrying 2 copies of the IPF risk gene FAM13A minor allele rs2609255 had significantly higher odds of a definite UIP pattern compared with the other patterns (OR 3.40, 95% CI 1.19-9.70), and compared with an alternative diagnosis (OR 3.65, 95% CI 1.25-10.65). We demonstrated a novel association between FAM13A and SSc-UIP. Contrary to IPF and RA-ILD, the MUC5B promoter polymorphism was not associated with a definite UIP pattern in SSc-ILD.

Bernstein EJ ，Boin F ，Elicker B ，Luo Y ，Ren Y ，Zhang M ，Varga J ，Assassi S ... -  《-》

Transthoracic Lung Ultrasound in Systemic Sclerosis-Associated Interstitial Lung Disease: Capacity to Differentiate Chest Computed-Tomographic Characteristic Patterns.

Rotondo C ，Busto G ，Rella V ，Barile R ，Cacciapaglia F ，Fornaro M ，Iannone F ，Lacedonia D ，Quarato CMI ，Trotta A ，Cantatore FP ，Corrado A ... -  《-》

Extent of lung fibrosis is of greater prognostic importance than HRCT pattern in patients with progressive pulmonary fibrosis: data from the ILD-PRO registry.

The prognostic value of patterns and quantitative measures of lung fibrosis on high-resolution computed tomography (HRCT) in patients identified as having progressive pulmonary fibrosis (PPF) has not been established. We investigated whether HRCT patterns and quantitative scores were associated with risk of progression in patients with PPF. Patients enrolled in the ILD-PRO Registry had an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis, reticular abnormality and traction bronchiectasis, and met criteria for ILD progression. HRCT images taken between 24 months prior to enrollment and 90 days after enrollment were analyzed using a machine learning algorithm to derive quantitative scores. Associations were assessed between HRCT pattern (usual interstitial pneumonia [UIP]-like versus other patterns) and tertiles of quantitative scores and measures of disease severity at enrollment, and between these patterns/tertiles at enrollment and ILD progression (relative decline in forced vital capacity [FVC] % predicted ≥ 10%, lung transplant, or death) over a median follow-up of 17.3 months. Among 395 patients, 178 (45.1%) had a UIP-like pattern on HRCT. A UIP-like pattern did not associate with worse disease severity at enrollment or an increased risk of ILD progression (HR 1.01 [95% CI: 0.71, 1.44]). The highest quantitative lung fibrosis (QLF) score tertile (≥ 20.5%) was associated with worse disease severity. In unadjusted analyses, patients with QLF scores in the highest tertile had a significantly increased risk of ILD progression versus the middle tertile (HR [95% CI] 1.63 [1.07, 2.49] and a numerically increased risk versus the lowest tertile (HR 1.46 [0.97, 2.18]); however, after adjustment for sex, age, FVC % predicted and oxygen use at enrollment, there were no significant differences. There were no significant associations between tertiles of quantitative ILD score, quantitative ground glass score, or quantitative honeycomb cysts score and risk of ILD progression in unadjusted or adjusted analyses. In a real-world cohort of patients with PPF, QLF score associated with subsequent risk of ILD progression, while HRCT pattern did not. The QLF score did not provide additional prognostic information beyond clinical variables. ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www. gov .

Swaminathan AC ，Weber JM ，Todd JL ，Palmer SM ，Neely ML ，Whelan TP ，Kim GHJ ，Leonard TB ，Goldin J ... -  《RESPIRATORY RESEARCH》

RS35705950 polymorphism of MUC5B Gene: Association with Rheumatoid Arthritis and Interstitial lung disease in Tunisian Population.

Saad A ，Baccouche K ，Fodha H ，Haj Khelil A ，Fakhfakh R ，Khalifa D ，El Amri N ，Saad A ，Bouajina E ... -  《-》

Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

Churg A ，Poletti V ，Ravaglia C ，Matej R ，Vasakova MK ，Hornychova H ，Stewart B ，Patel D ，Duarte E ，Gomez Manjarres DC ，Mehta HJ ，Vaszar LT ，Tazelaar H ，Wright JL ... -  《-》