Журнал болезней легких и лечения

Objective: To systematically review the use of azathioprine as a treatment for connective tissue diseaseassociated interstitial lung disease (CTD-ILD) in terms of effectiveness and safety.

Materials and methods: A literature search was performed using the PubMed, EMBASE, CINAHL, Cochrane, and Scopus databases. The search was restricted to articles published in English from 1950 to March 2018 that examined the use of azathioprine in patients with CTD-ILD and determined its effects on a primary or secondary endpoint. This review included studies that measured the impacts of azathioprine in terms of effectiveness and safety.

Results: The search identified 15 studies with a total of 424 subjects. Two hundred twenty patients received azathioprine. A majority of the studies failed to provide clear evidence for the effectiveness of azathioprine. The reported adverse events were: death 4.5% (n=10), infection 1.3% (n=3), myelosuppression 0.9% (n=2), and malignancy 0.45% (n=1). The rate of azathioprine discontinuation due to treatment failure was 2.7% (n=6).

Conclusions: No clear impacts of azathioprine have been reported, yet this review reveals that the drug is less useful than previously believed. In contrast to our current knowledge, this review suggests that the ILD histopathological pattern appears to be the most important determinant of treatment responses and prognosis, and treatment decisions should be based on this parameter, rather than the background CTD. AZA is a relatively safe option. More well-designed studies are needed. The recruitment of subjects based on the ILD pattern rather than CTD may produce more consistent results.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent cessations of breathing due to obstruction of the upper respiratory tract. Obesity and OSA often coexist and obesity may be a major risk factor for worsening OSA. Both are associated with several comorbidities such as hypertension, cardiovascular disease and cerebrovascular accidents. There are biomarkers that are shared between both obesity and OSA with some being more sensitive for OSA. To better understand the relationship of the biomarkers associated specifically with OSA, a more comprehensive review of OSA biomarkers compared to previous literature was conducted with the goal of determining whether OSA is an individual risk factor. Specifically, OSA patients were matched based on BMI to controls with no comorbidities to rule out confounders. Furthermore, it was investigated if continuous positive airway pressure (CPAP) therapy was effective in reducing these biomarkers. OSA was shown to be an individual associated risk factor, compared to obesity, for further changes in biomarkers related to inflammatory changes (Il-8, TNF- a, IL-6, INF-y), epithelial and cellular receptor regulation (ICAM-1, VCAM-1, P-Selectin, TLR-2 and TLR-4), atherosclerosis biomarkers and anatomical changes (increased CIMT, pulse wave velocity, catecholamines, aortic pulse velocity index), diabetes (HbA1c, insulin resistance) and hypertension (sFLT-1, sEng, YKL-40). This review revealed that biomarkers are significantly associated with OSA independent from obesity. CPAP treatment resulted in a reduction of these biomarkers.