A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS).

BACKGROUND: Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed. METHOD/DESIGN: A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test. ETHICS/DISSEMINATION: This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations. TRIAL REGISTRATION: Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022-07-12, 1401/04/21.

A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications.

Lung cancer is the deadliest malignancy worldwide. An inflammatory microenvironment is a key factor contributing to lung tumor progression. Tumor-Associated Macrophages (TAMs) are prominent components of the cancer immune microenvironment with diverse supportive and inhibitory effects on growth, progression, and metastasis of lung tumors. Two main macrophage phenotypes with different functions have been identified. They include inflammatory or classically activated (M1) and anti-inflammatory or alternatively activated (M2) macrophages. The contrasting functions of TAMs in relation to lung neoplasm progression stem from the presence of TAMs with varying tumor-promoting or anti-tumor activities. This wide spectrum of functions is governed by a network of cytokines and chemokines, cell-cell interactions, and signaling pathways. TAMs are promising therapeutic targets for non-small cell lung cancer (NSCLC) treatment. There are several strategies for TAM targeting and utilizing them for therapeutic purposes including limiting monocyte recruitment and localization through various pathways such as CCL2-CCR2, CSF1-CSF1R, and CXCL12-CXCR4, targeting the activation of TAMs, genetic and epigenetic reprogramming of TAMs to antitumor phenotype, and utilizing TAMs as the carrier for anti-cancer drugs. In this review, we will outline the role of macrophages in the lung cancer initiation and progression, pathways regulating their function in lung cancer microenvironment as well as the role of these immune cells in the development of future therapeutic strategies.

Case 281: Thoracic Air Leak Syndrome in a Patient with Hematopoietic Stem Cell Transplantation and Graft-versus-Host Disease.

HistoryAn 18-year-old man was diagnosed with precursor B-cell lymphoblastic leukemia and underwent transplantation of hematopoietic stem cells from his human leukocyte antigen-matched sister 1 year prior to admission. He was admitted to evaluate progressive shortness of breath and dry cough of 1-month duration. He did not report fever, night sweats, or hemoptysis. Physical examination revealed he was afebrile and had normal pulse oxygen saturation. The examination revealed crepitation on palpation of the anterior neck, expiratory wheezes, and crackles heard at auscultation of bases of both lungs. Extensive maculopapular rash on the skin was consistent with graft-versus-host disease (GVHD). Laboratory tests revealed elevated liver transaminase and bilirubin levels that were attributed to liver GVHD. Nonenhanced thin-section CT of the chest was performed.

Case 281.

History An 18-year-old man was diagnosed with precursor B-cell lymphoblastic leukemia and underwent transplantation of hematopoietic stem cells from his human leukocyte antigen-matched sister 1 year prior to admission. He was admitted to evaluate progressive shortness of breath and dry cough of 1-month duration. He did not report fever, night sweats, or hemoptysis. Physical examination revealed he was afebrile and had normal pulse oxygen saturation. The examination revealed crepitation on palpation of the anterior neck, expiratory wheezes, and crackles heard at auscultation of bases of both lungs. Extensive maculopapular rash on the skin was consistent with graft-versus-host disease (GVHD). Laboratory tests revealed elevated liver transaminase and bilirubin levels that were attributed to liver GVHD. Nonenhanced thin-section CT of the chest was performed (Figs 1-5).