Comparison of pulmonary and small airways function between idiopathic inflammatory myopathies patients with and without interstitial lung disease.

OBJECTIVES: To evaluate pulmonary and small airway function in patients with idiopathic inflammatory myopathies (IIM) and make comparisons between patients with and without interstitial lung disease (ILD). METHODS: Newly diagnosed IIM patients with and without ILD determined by high resolution computed tomography were included in the study. Pulmonary and small airway function was assessed by spirometry, diffusing capacity for carbon monoxide (DLCO), body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry and measurement of respiratory resistance by the interrupter technique (Rint) using the Q-box system. We used discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography to evaluate for small airway dysfunction. RESULTS: Study cohort comprised of 26 IIM patients, 13 with and 13 without ILD. IIM-ILD patients presented more frequently with dyspnoea, fever, arthralgias and positive anti-synthetase antibodies, compared to IIM patients without ILD. Classic spirometric parameters and most lung physiology parameters assessing small airway function did not differ between the two groups. Predicted total lung capacity and residual volume (TLCN2WO, RVN2WO) measured by multiple breath nitrogen washout and the TLCN2WO/TLCpleth ratio were significantly lower in IIM-ILD patients compared to those without ILD (mean: 111.1% vs. 153.4%, p=0.034, median: 171% vs. 210%, p=0.039 and median: 1.28 vs. 1.45, p=0.039, respectively). Rint tended to be higher among IIM-ILD patients (mean:100.5% vs. 76.6%, p=0.053). CONCLUSIONS: Discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography in IIM-ILD patients indicate an early small airways dysfunction in these patients.

Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic implications.

Bone erosions develop early in the course of rheumatoid arthritis (RA) and deteriorate progressively, causing joint damage and resulting in impaired functional capacity of patients. During the last years, considerable number of studies has increased our understanding of the pathogenetic mechanisms mediating the development of bone erosions in RA. Increased production of RANKL and other cytokines, dysregulation of innate immune mechanisms, autoantibodies specific to RA and alterations of microRNA expression stimulate differentiation and function of osteoclasts, which are responsible for the development of bone erosions. Besides, increased levels of cytokines, overproduction of antagonists of the canonical Wnt signaling pathway and deficient production of bone morphogenetic proteins result in impaired osteoblast differentiation and function, undermining the capacity of bone erosions to repair. Disease-modifying antirheumatic drugs, synthetic or biological, currently used in the treatment of RA, can halt the progression of bone erosions and may even lead to partial repair, although complete repair is unattainable. Targeting pathogenetic mechanisms participating in the erosive process may add to the therapeutic effect of DMARDs and help in the prevention or repair of bone erosions. However, more studies are still needed to confirm whether such therapeutic strategies are effective.

Small airways dysfunction in patients with systemic sclerosis and interstitial lung disease.

Background: A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). Methods: This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5-R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Results: Phase III slopeN2SBW and R5-R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5-R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5-R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Conclusion: Phase III slopeN2SBW and R5-R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.

The Involvement of MicroRNAs in Osteoarthritis and Recent Developments: A Narrative Review.

BACKGROUND: Osteoarthritis (OA) is the most common chronic joint disease and it may progressively cause disability and compromise quality of life. Lately, the role of miRNAs in the pathogenesis of OA has drawn a lot of attention. miRNAs are small, single-stranded, non-coding molecules of RNA which regulate gene expression at post-transcriptional level. The dysregulation of the expression of several miRNAs affects pathways involved in OA pathogenesis. OBJECTIVE: The purpose of this article is to review the literature on the involvement of miRNAs in the pathogenesis of OA and the implications on its diagnosis and treatment. MATERIALS AND METHODS: An extensive electronic literature search was conducted by two researchers from January 2008 to August 2017. Titles and abstracts of papers were screened by the authors for further inclusion in the present work. Finally, full texts of the selected articles were retrieved. RESULTS: Abnormally expressed miRNAs enhance the production of cartilage degrading enzymes, inhibit the expression of cartilage matrix components, increase the production of proinflammatory cytokines, facilitate chondrocyte apoptosis, suppress autophagy in chondrocytes and are involved in pain-related pathways. miRNAs are also incorporated in extra-cellular membranous vesicles such as exosomes and participate in the intercellular communication in osteoarthritic joints. CONCLUSION: Ongoing research on miRNAs has potential implications in the diagnosis and treatment of OA. Their different levels in peripheral blood and synovial fluid between OA patients and healthy population makes them candidates for being used as biomarkers of the disease, while targeting miRNAs may be a novel therapeutic strategy in OA.