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1.  Shrinking Lung Syndrome as a Manifestation of Pleuritis: A New Model Based on Pulmonary Physiological Studies 
The Journal of rheumatology  2013;40(3):273-281.
Objectives
The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients.
Methods
Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantitate lung volume and parenchymal density.
Results
Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging was free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density.
Conclusion
Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with two characteristic physiological abnormalities: 1) impaired respiratory force at high but not low lung volumes, and 2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example via neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.
doi:10.3899/jrheum.121048
PMCID: PMC4112073  PMID: 23378468
Shrinking Lung Syndrome; Pleuritis; Pleurisy; Systemic Lupus Erythematosus; Lung
2.  Extrapulmonary Manifestations of Sarcoidosis 
doi:10.1016/j.rdc.2013.02.007
PMCID: PMC3756667  PMID: 23597964
Sarcoidosis; Extrapulmonary; Granulomas; Granulomatous; Löfgren syndrome; Neurosarcoidosis
3.  Meta-analysis in granulomatosis with polyangiitis reveals shared susceptibility loci with rheumatoid arthritis 
Arthritis and rheumatism  2012;64(10):3463-3471.
Objectives
To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis), and determine whether genetic susceptibility profiles of other autoimmune diseases are associated with GPA
Methods
Genetic data from two cohorts were meta-analyzed. Genotypes for 168 previously identified single nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained for a total of 880 GPA cases and 1969 controls of European descent. Single marker associations were identified using additive logistic regression models. Multi-SNP associations with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn’s disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses using ancestry informative markers and principal components analysis.
Results
Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (OR 0.79. 95% CI 0.70–0.89, p=9.8×10−5). A genetic risk score based on rheumatoid arthritis susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02–1.08, p=5.1×10−5).
Conclusions
Rheumatoid arthritis and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically associated with GPA in this study.
doi:10.1002/art.34496
PMCID: PMC3425721  PMID: 22508400
genetics; vasculitis; granulomatosis with polyangiitis; rheumatoid arthritis; CTLA4
4.  Alpha1-Antitrypsin Deficiency–Related Alleles Z and S and the Risk of Wegener’s Granulomatosis 
Arthritis and rheumatism  2010;62(12):3760-3767.
Objective
Deficiency of α1-antitrypsin (α1AT) may be a determinant of susceptibility to Wegener’s granulomatosis (WG). Several previous, mainly small, case–control studies have shown that 5–27% of patients with WG carried the α1AT deficiency Z allele. It is not clear whether the S allele, the other major α1AT deficiency variant, is associated with WG. This study investigated the relationship of the α1AT deficiency Z and S alleles with the risk of developing WG in a large cohort.
Methods
We studied the distribution of the α1AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods.
Results
Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2-parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98–2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33–∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele.
Conclusion
Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α1AT deficiency and susceptibility to WG.
doi:10.1002/art.27742
PMCID: PMC3123032  PMID: 20827781
6.  Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials 
Thorax  2013;69(5):436-444.
Rationale
Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.
Methods
The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).
Results
A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.
Conclusion
Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
doi:10.1136/thoraxjnl-2013-204202
PMCID: PMC3995282  PMID: 24368713
Connective tissue disease associated lung disease; Interstitial Fibrosis; Idiopathic pulmonary fibrosis; Rheumatoid lung disease; Systemic disease and lungs

Results 1-6 (6)