Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease whose diagnosis often requires surgical lung biopsies (SLB) in cases without consistent radiological findings. We previously published that the expression of the chemokine receptors CXCR3 and CCR4 on T cells is significantly different in bronchoalveolar lavage (BAL) of IPF patients from other interstitial lung diseases. The aim of the study was to evaluate cut-off values of CXCR3 and CCR4 receptors expressed on bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells useful for a differential diagnosis. Methods: Ninety-three patients were enrolled: 35 IPF, 36 interstitial lung diseases (nIPF) and 22 sarcoidosis. CXCR3 and CCR4 were evaluated on BAL and PB T lymphocytes with flow cytometry. Results: Among PB and BAL variables considered, the values of the ratio of BAL and PB CXCR3 on CD4 cells were clustered in the most informative way to obtain a classification rule for the diagnosis of patients without steroid therapy (n = 66/93). Patients with a CXCR3 ratio BAL/PB on CD4 T cells lower or equal than 1.43 were assigned to the IPF group with sensitivity = 0.87 and specificity = 0.90. All the other variables considered showed lower sensitivity and specificity in discriminating IPF patients. Conclusions: The evaluation of chemokine receptors on BAL and PB T lymphocytes could aid to discriminate IPF in subjects without steroid therapy, particularly in those patients with a high-resolution computed tomography (HRCT) non typical for Usual Interstitial Pneumonia (UIP). (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 35-43).

Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy.

BACKGROUND: Venom immunotherapy is an effective method for the treatment of Hymenoptera venom allergy. Different extracts and treatment schedules are available. OBJECTIVE: To compare the safety and efficacy of immunotherapy in 3 cohorts of patients sensitized to Vespula species. METHODS: In this open study, 43 patients were treated with a subcutaneous aqueous extract for induction and maintenance (AA), 34 with a subcutaneous depot extract for induction and maintenance (DD), and 29 with subcutaneous aqueous and subcutaneous depot extracts for induction and maintenance, respectively (AD). Cluster schedules were followed to reach maintenance, and adverse effects during treatment and after naturally occurring stings were recorded. RESULTS: Depot immunotherapy was better tolerated mainly owing to the lower frequency of local adverse effects in the induction phase (5.9% vs 42.5% and 1.3% vs 5.1% on a per patient and per dose basis, respectively; P < .001 for both) and for effects occurring within 60 minutes after vaccination (2.9% vs 19.2% and 0.2% vs 2.8% on a per patient and per dose basis; P = .03 and P < .001, respectively). Furthermore, 19 of 20 AA, 9 of 9 AD, and 10 of 10 DD patients who were restung experienced only minor local effects. CONCLUSIONS: Venom immunotherapy is efficacious. Although there was no decrease in systemic reactions, depot immunotherapy to Vespula venom induced fewer early local adverse effects. Patients undergoing an induction phase with an aqueous extract can benefit from switching to a depot extract during maintenance. Increasing the flexibility of the immunization schedules may improve compliance with this potentially lifesaving treatment.

Safety and pharmacoeconomics of a cluster administration of mite immunotherapy compared to the traditional one.

Accelerated schedules of administration of immunotherapy (rush or clustered) allow to reach the maintenance dosage in shorter times with respect to traditional schedules. Nowadays formal assessments of the safety and economic aspects of those schedule lack for inhalant allergens. We compared in a prospective randomized open study a cluster and a traditional immunotherapy with standardized mite extracts. Thirty eight adult patients with persistent allergic rhinitis due to mites were randomized to receive either a traditional (N= 19) or a cluster (N=19) up-dosing scheme, lasting 13 and 3 weeks respectively. Side effects were carefully evaluated and recorded by physician and costs were calculated as well. In the cluster and traditional updosing 148 and 241 injections were given respectively. With the cluster up-dosing there were 8 local reactions (15.9% of patients and 5.4% of injections). With the traditional schedule 6 local reactions (31.5 % of patients and 2.4% of injections) occurred. There was no difference between the two treatments in occurrence of side effects per patient and per injection (chi-square 1.31 and 2.23, p= NS). No systemic reaction was recorded. Considering the cost of the extract, the cost of injections and the time spent, the cluster regimen resulted in a global spare of 244.95 euros per patient in the build-up phase. The cluster up-dosing is as safe as the traditional one and allows a significant economical save.