Interleukin-18: A Novel Participant in the Occurrence, Development, and Drug Therapy of Obliterative Bronchiolitis Postlung Transplantation

Background. Obliterative bronchiolitis (OB) was a main cause of deterioration of long-term prognosis in lung transplant recipients after the first posttransplant year. Proinflammatory cytokine interleukin-18 (IL-18) strengthened both the natural immunity and acquired immunity and played an important role in organ transplantation. The roles of IL-18 in the occurrence, development, and drug treatment of OB remained unclear. Methods. Small interfering RNA (siRNA) against mouse IL-18 (siRNA-IL-18) was used to silence IL-18 expression. Mouse heterotopic tracheal transplantation model was used to simulate OB. Recipient mice were divided into 5 groups ( n = 12 ) according to donor mouse strains and drug treatment: isograft group, allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group. The luminal obliteration rates were pathological evaluation. Expressions of cytokines and MMPs were detected by real-time PCR, western blot, and enzyme chain immunosorbent assay (ELISA). Results. The luminal obliteration rates of IL-18 of the siRNA-IL-18 group were significantly lower than those of the negative control group ( p < 0.0001 ) and the blank control group ( p = 0.0002 ). mRNA expressions of IFN-γ, EMMPRIN, MMP-8, and MMP-9 of the siRNA-IL-18 group were significantly lower than those of the negative and blank control groups. No tracheal occlusion occurred in grafts of the isograft group. The rates of tracheal occlusion of the allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group were 72.17 ± 4.66 %, 40.33 ± 3.00 %, 38.50 ± 2.08 %, and 23.33 ± 3.24 %, respectively. There were significant differences between the 4 groups ( p < 0.001 ). Serum protein expressions of IL-17 ( p = 0.0017 ), IL-18 ( p = 0.0036 ), IFN-γ ( p = 0.0102 ), and MMP-9 ( p = 0.0194 ) were significantly decreased in the allograft+tacrolimus+azithromycin group compared to the allograft group. Conclusions. IL-18 could be a novel molecular involved in the occurrence, development, and drug treatment of OB.

A young lady with dyspnoea: Quest for the cause

Pulmonary hypertension (PH) is a common cause of dyspnoea. The management and prognosis of PH varies with the underlying aetiology. Hence the detection of the cause of PH is important. Obliterative bronchiolitis (OB) is a common but under-recognised cause of PH. OB is usually secondary to childhood infections known as post-infectious OB. It can also be secondary to other diseases, but cryptogenic OB is an extremely rare entity. Here we share a unique case of PH due to cryptogenic OB and its successful outcome with optimal management.

Tutto quello che il pediatra dovrebbe sapere sul mepolizumab

Mepolizumab, a monoclonal antibody blocking IL-5, is efficacious in the treatment of severe lung diseases sharing eosinophilic inflammation pattern. The paper describes two cases in which the drug was used with excellent results. The first involved a 14-year-old boy with obliterative bronchiolitis, the other an 11-year-old girl with non-atopic asthma. Both cases shared the eosinophilic phenotype of the disease, defined by an eosinophilic count in the peripheral blood equal to or greater than 2% (i.e. a baseline value of 150-200 cells/µl or 300 cells/µl during the previous year). Its use demonstrates clinical improvement in severe refractory asthma with eosinophilic phenotype and as off-label drug in obliterative bronchiolitis, leading to a decrease in the rate of exacerbations and enabling the reduction of corticosteroids as well as the resolution of structural anomalies, respectively.

Case Report: Flavoring-Related Lung Disease in a Coffee Roasting and Packaging Facility Worker With Unique Lung Histopathology Compared With Previously Described Cases of Obliterative Bronchiolitis

Occupational exposure to diacetyl, a butter flavor chemical, can result in obliterative bronchiolitis. Obliterative bronchiolitis is characterized by exertional dyspnea, fixed airflow obstruction, and histopathologic constrictive bronchiolitis, with bronchiolar wall fibrosis leading to luminal narrowing and obliteration. We describe a case of advanced lung disease with histopathology distinct from obliterative bronchiolitis in a 37-year-old male coffee worker following prolonged exposure to high levels of diacetyl and the related compound 2,3-pentanedione, who had no other medical, avocational, or occupational history that could account for his illness. He began working at a coffee facility in the flavoring room and grinding area in 2009. Four years later he moved to the packaging area but continued to flavor and grind coffee at least 1 full day per week. He reported chest tightness and mucous membrane irritation when working in the flavoring room and grinding area in 2010. Beginning in 2014, he developed dyspnea, intermittent cough, and a reduced sense of smell without a work-related pattern. In 2016, spirometry revealed a moderate mixed pattern that did not improve with bronchodilator. Thoracoscopic lung biopsy results demonstrated focal mild cellular bronchiolitis and pleuritis, and focal peribronchiolar giant cells/granulomas, but no evidence of constrictive bronchiolitis. Full-shift personal air-samples collected in the flavoring and grinding areas during 2016 measured diacetyl concentrations up to 84-fold higher than the recommended exposure limit. Medical evaluations indicate this worker developed work-related, airway-centric lung disease, most likely attributable to inhalational exposure to flavorings, with biopsy findings not usual for obliterative bronchiolitis. Clinicians should be aware that lung pathology could vary considerably in workers with suspected flavoring-related lung disease.