肺部疾病与治疗杂志

Leukotriene receptor antagonist (LTRA) montelukast is frequently used for breathing difficulties associated with sleep, allergic rhinitis, and asthma. Recent investigations have documented a number of negative outcomes in kids, including neuropsychiatric problems and sleep difficulties. Objective: To learn more about the safety profile of montelukast for kids with allergies, hay fever, and breathing problems related to sleep. Method and findings: Over a two-year period, we retrospectively examined all adverse medication reactions to montelukast among 385 kids aged 6 months and older in six tertiary centres. 89.6% of patients had asthma, 50% had allergic rhinitis, and 13.6% had breathing problems linked to sleep. Singulair was the most widely used form of montelukast, accounting for 67.9% of all prescriptions. According to this study, there were 123 individuals who experienced adverse medication responses, and the majority of them were in those toddlers (22.8%) and those between the ages of 4 and 9 (52.8%) were the next two age groups. 9.8% of the children had two (ADRs) documented, whereas 5.5% had three or more. The most frequent adverse drug reactions (ADRs), which affected 15.1% of participants (overlap was widespread; 5.5% of kids had trouble sleeping, 4.4% had trouble falling asleep or staying asleep, and 1.82% had nightmares), were agitation (10.4%), pain (9.4%), and hyperactivity (6.8%).

The proliferation and self-renewal of alveolar macrophages (AM) are significant components of the microenvironment of lung tissue. The effect of immune cells, particularly neutrophils, on the homeostasis or functionality of AM is not fully understood. In this investigation, we used CXCL1 to promote neutrophil in vivo migration into bronchoalveolar lavage (BAL) fluid and lung, and we co-cultured these cells with AMs in vitro. It was discovered that BAL neutrophils (BAL-neutrophils) as opposed to BM-neutrophils limit AM growth. An analysis of data that was made accessible to the public revealed that there was significant molecular heterogeneity between blood and BM neutrophils and lung neutrophils. Unexpectedly, BAL-neutrophils from mice infected with the influenza virus PR8 (PR8-neutrophils) did not prevent the growth of AMs. Additionally, bulk RNA sequencing demonstrated that co-culturing AMs with PR8 neutrophils caused IFN- to be produced. In addition, BAL neutrophils from mice infected with PR8 altered the polarisation and phagocytosis of AMs and AMs co-cultured with BAL neutrophils had increased expression of metabolism- and ROS-associated genes. Combining inhibitors of various neutrophil death mechanisms reversed the inhibition of AM growth by BAL-neutrophils. Our findings imply that different neutrophil cell death processes control the proliferation of AMs. An alternative therapeutic approach for enhancing AM homeostasis in respiratory diseases may involve targeting neutrophil death.