We produced ovalbumin (OVA)-sensitized rats as an animal model of nasal allergy. Intranasal instillation of OVA induced hypertrophic and metaplastic changes of goblet cells in nasal epithelium of OVA- sensitized rats. Intraepithelial mucosubstance in nasal mucosa increased significantly at 24 h after 3 or 7 d of OVA instillation, accompanied by mucosal infiltration of eosinophils. The effects of H1-antagonist (d-chlorpheniramine malate), H2-antagonist (cimetidine), dexamethasone, indomethacin, cysteinyl leukotrienes (cysLTs)-antagonist (ONO1078), and antirat neutrophil antiserum on OVA-induced changes were examined. Mucus production was significantly inhibited by dexamethasone, and ONO1078, whereas eosinophil infiltration was significantly inhibited by H1-antagonist, dexamethasone, and anti-rat neutrophil antiserum. These results indicate that cysLTs (LTs C4, D4, and E4) may play an important role in antigen-induced mucus production, and that eosinophil infiltration does not relate to mucus production. Intranasal instillation of lipopolysaccharide (LPS) also induced intraepithelial mucus production, and it was significantly inhibited by dexamethasone, indomethacin, and antirat neutrophil antiserum; however, cysLTs antagonist had no effect on LPS-induced change. These results indicate that neutrophil and cyclooxygenase products are important in LPS-induced mucus production, and there are different mechanisms of mucus production between allergic inflammation and LPS stimulation.
Background
The proportion of tuberculosis (TB) patients who are older adults is increasing worldwide. Nearly 60% of TB patients in Japan are 70 years or older, and the TB incidence rate in Japan is one of the highest among high-income countries. The previous TB treatment guidelines prior to 2018 in Japan recommended excluding pyrazinamide (PZA) from the initial regimen for patients aged over 80 years.
Objectives
We aimed to examine differences in TB treatment outcomes among different age groups, and between those who received PZA and those who did not.
Methods
We performed a retrospective cohort study of patients with pulmonary TB who were managed at a single medical center in Japan. We compared treatment outcomes and adverse events that resulted in treatment interruption across the age groups.
Results
Of 246 patients, 117 (48%) were aged 75 years or older. Compared with patients aged < 74 years, those ≥ 75 years were less likely to have PZA in the initial regimen (53.0% vs 89.9%;
p
< 0.0001), more likely to die during treatment (38.5% vs 6.2%;
p
< 0.0001), and more likely to experience adverse events (30.8% vs 19.4%;
p
< 0.05). The mortality rate related to TB at 2 months after TB treatment initiation was 28% in those aged ≥ 84 years. Furthermore, among patients aged ≥ 84 years, those who did not receive PZA were significantly more likely to die than those who did (65.8% vs 36.8%;
p
< 0.05).
Conclusions
Patients aged ≥ 75 years with pulmonary TB experienced increased mortality related to TB during treatment and more frequent adverse events than younger patients, even though PZA was often avoided among older patients.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40266-021-00880-4.
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