Efficacy and Safety of Masitinib in Corticosteroid-Dependent Severe Asthma: A Randomized Placebo-Controlled Trial.

Background: Masitinib is an oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor (PDGFR) signaling, both of which are implicated in various mechanisms of asthma pathogenesis. Objective: Assessment of masitinib as an add-on to standard maintenance therapy as compared with placebo in the treatment of oral corticosteroid-dependent severe asthma. Methods: We conducted a randomized (2:1), placebo-controlled study of masitinib (6 mg/kg/d) in adults with severe asthma uncontrolled by high dose inhaled corticosteroids and long-acting beta-adrenoreceptor agonists plus oral corticosteroids (OCS) (≥7.5 mg/d). No minimum baseline blood eosinophil count was specified. Following a protocol amendment, the primary endpoint was reduction of annualized severe asthma exacerbation rate adjusted for the overall time on treatment (SAER). Subgroup analysis according to yearly cumulative OCS intake was also performed, a higher OCS dose indicating more severe asthma that is harder to control. Results: Following an average exposure of approximately 13 months, masitinib (n = 240) reduced the SAER by 35% relative to placebo (n = 115) (rate ratio (RR) 0.65 (95% CI [0.47-0.90]; P = 0.010)). For patients with eosinophil ≥150 cell/µL, masitinib (n = 181) reduced SAER by 38% relative to placebo (n = 87); RR 0.62 (95% CI [0.42-0.91]; P = 0.016). Benefit of masitinib was shown to increase in the most severely affected patients (OCS intake of >1000 mg/year), with a significant (P < 0.01) reduction in SAER of 50%-70%. Safety was consistent with the known masitinib profile. Conclusion: Orally administered masitinib reduces the risk of asthma exacerbations in severe asthma patients, with an acceptable safety profile. Masitinib may potentially provide a new treatment option for oral corticosteroid-dependent severe asthma.

Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in Various Respiratory Diseases: A Retrospective Analysis.

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio are two extensively used inflammatory markers that have been proved very useful in evaluating inflammation in several diseases. The present article aimed to investigate if they have any value in distinguishing among various respiratory disorders. One hundred and forty-five patients with coronavirus disease 2019 (COVID-19), 219 patients with different chronic respiratory diseases (interstitial lung disease, obstructive sleep apnea(OSA)-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiectasis) and 161 healthy individuals as a control group were included in the study. While neither NLR nor PLR had any power in differentiating between various diseases, PLR was found to be significant but poor as a diagnostic test when the control group was compared with the OSA-COPD group. NLR was found to be significant but poor as a diagnostic test when we compared the control group with all three groups (separately): the OSA-COPD group; interstitial lung disease group, and bronchiectasis group. NLR and PLR had poor power to discriminate between various respiratory diseases and cannot be used in making the differential diagnosis.

The reliability of lung ultrasound in assessment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the severest form of idiopathic interstitial pneumonia, with a median survival time estimated at 2-5 years from the time of diagnosis. It occurs mainly in elderly adults, suggesting a strong link between the fibrosis process and aging. Although chest high-resolution computed tomography (HRCT) is currently the method of choice in IPF assessment, diagnostic imaging with typical usual interstitial pneumonia (UIP) provides definitive results in only 55%, requiring an invasive surgical procedure such as lung biopsy or cryobiopsy for the final diagnostic analysis. Lung ultrasound (LUS) as a noninvasive, non-radiating examination is very sensitive to detect subtle changes in the subpleural space. The evidence of diffuse, multiple B-lines defined as vertical, hyperechoic artifacts is the hallmark of interstitial syndrome. A thick, irregular, fragmented pleura line is associated with subpleural fibrotic scars. The total numbers of B-lines are correlated with the extension of pulmonary fibrosis on HRCT, being an LUS marker of severity. The average distance between two adjacent B-lines is an indicator of a particular pattern on HRCT. It is used to appreciate a pure reticular fibrotic pattern as in IPF compared with a predominant ground glass pattern seen in fibrotic nonspecific interstitial pattern. The distribution of the LUS artifacts has a diagnostic value. An upper predominance of multiple B-lines associated with the thickening of pleura line is an LUS feature of an inconsistent UIP pattern, excluding the IPF diagnosis. LUS is a repeatable, totally radiation-free procedure, well tolerated by patients, very sensitive in detecting early changes of fibrotic lung, and therefore a useful imaging technique in monitoring disease progression in the natural course or after initiation of treatment.

[Analysis of the national tuberculosis program. Evolution of tuberculosis in Bihor district, Romania]. / Analiza impactului programului national de control al tuberculozei asupra evolutiei tuberculozei în judetul Bihor.

The prevention and control of tuberculosis are made by a special network, covering all the sanitary units and the entire medical staff. Ten years ago, the DOTS strategy (Directly Observed Treatment, Short-course) was enacted and the National Program for tuberculosis control (PNCT) was implemented on "medium terms" (1997-2000 and after that 2001-2005), with results in 2003 when, for the first time after two decades, has been observed a decrease of the incidence of tuberculosis, maintained also during the next years. The national program of health - the Supervising and control of tuberculosis, in Bihor district rolled in good terms, without any problems in achieving the proposed aims, due to the good coordination between institutions and professionals directly involved in the surveillance and control of disease. As a result of PNCT and prophylactic programs, there was a long-term diminish of costs associated to health care and a medium-term improvement of the following variables: incidence, mortality caused by TB, rate of readmissions, rate of therapeutic success of new TB cases with positive microscopy / new culture-positive TB cases, rate of diagnosis of new pulmonary TB cases with positive microscopy.