Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.
Large differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS‐CoV‐2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS‐Cov‐2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT
1
R) axis associated with oxidative stress. This leads to insulin resistanceas well as lung and endothelial damage, two severe outcomes of COVID‐19. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT
1
R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are given: Kimchi in Korea, westernized foods and the slum paradox. It is proposed that fermented cabbage is a proof‐of‐concept of dietary manipulations that may enhance Nrf2‐associated antioxidant effects helpful in mitigating COVID‐19 severity.
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