Evidence for the contribution of neutrophils to the pathogenesis of pulmonary emphysema is not convincing. We evaluated neutrophil involvement in subclinical pulmonary emphysema by measuring human neutrophil lipocalin (HNL) and two matrix metalloproteinases, gelatinase B (MMP-9) and neutrophil collagenase (MMP-8), in bronchoalveolar lavage fluid (BALF) from 65 community-based older volunteers. HNL is a recently isolated 24-kD protein secreted from secondary granules of activated neutrophils. Despite no appreciable increase in the number of neutrophils, the level of HNL was significantly increased in BALF from subjects with emphysema evidenced by computed tomography regardless of current smoking, as compared with smokers without emphysema. The levels of MMP-9 and MMP-8 were also significantly higher in current smokers with emphysema than in those without emphysema. The appearance of a 130-kD HNL/MMP-9 complex on gelatin zymography and HNL immunoblot indicated neutrophils to be a significant source of MMP-9 in the subjects' BALF. In a 24-h culture medium of alveolar macrophages, only a latent form of MMP-9 was detected, and there was no difference in the level of MMP-9 between the groups. These data provide further evidence for neutrophil involvement in subclinical pulmonary emphysema.

aaProtease-antiprotease imbalance theory has been a central theme for the last 30 years in the study of the pathogenesis of pulmonary emphysema [1,2]. Although smoking is a major exogenous cause of pulmonary emphysema, only a small percentage of smokers develop clinically apparent pulmonary emphysema. Numerous studies have examined the effect of cigarette smoking on the proteaseantiprotease balance in body fluids, but few have focused on individual differences in the susceptibility to pulmonary emphysema. Most studies have simply compared smokers and nonsmokers [3,4] or healthy subjects and patients with chronic obstructive pulmonary disease (COPD), mostly clinically diagnosed through pulmonary function tests [5]. However, the data from subjects with established COPD could be influenced by possible concomitant infections of the respiratory tract.It was previously demonstrated that neutrophil elastase (NE) complexed with α 1 -protease inhibitor (α 1 -PI; NE-α 1 -PI complex) in bronchoalveolar lavage (BAL) fluid was significantly increased in community-based older volunteers who had subclinical emphysema, as evidenced by lung computed tomographic (CT) scans, compared with those who had a comparable smoking history but no evidence of emphysema [6]. In addition, the releasability of NE from alveolar macrophages (AM) was shown to be high in those subjects with emphysema [7]. FINLAY et al. [8] recently reported that the levels of collagenase and gelatinase B in BAL fluid from subjects with clinically apparent emphysema were significantly higher than in healthy subjects.Another important class of proteases which is a candidate for causing chronic pulmonary destruction consists of the cysteine proteases, one of which, cathepsin L, has potent elastolytic activity at acidic pH [9,10] and is capable of inactivating α 1 -PI catalytically [11]. The expression of cathepsin L messenger ribonucleic acid (mRNA), as well as the activity of cathepsin L, was reported to be higher in BAL cells from smokers than in nonsmokers [12]. It is also possible that chronic smoking may decrease the level of cystatin C, an inhibitor of cathepsin L in the lungs, so that emphysematous changes are more likely to occur [13]. However, to our knowledge, there have been no reports on the levels of cathepsin L and cystatin C in BAL fluid from subjects with subclinical emphysema.In this study, the activities and immunological quantities of cathepsin L and cystatin C in BAL fluid from asymptomatic community-based older volunteers were evaluated and the releasability of cathepsin L from AM was examined in vitro. Cathepsin B was also measured in BAL fluid, which has little elastolytic activity. In particular, the Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. K. Takeyabu, T. Betsuyaku, M. Nishimura, A. Yoshioka, M. Tanino, K. Miyamoto, Y. Kawakami. ©ERS Journals Ltd 1998. ABSTRACT: This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in com...

Recently, it was reported that gene polymorphism for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the first‐pass metabolism of epoxide intermediates, was associated with susceptibility to emphysema. This association was examined in a Japanese population, performing polymerase chain reaction (PCR)‐based direct sequencing and restriction fragment length polymorphism assays for variant forms of mEPHX. The subjects consisted of 79 smokers with moderate to severe emphysema diagnosed by lung computed tomography scans, 58 smokers without emphysema, with a comparable smoking history, and 114 consecutive subjects who undertook annual health checkups. The allele frequency of exon 3 Tyr113 to His113, which was reported to confer slow mEPHX activity, was substantially higher in the population control group compared with that of the Caucasian control subjects in a previous study. However, neither the genotype distribution of exon 3, nor that of exon 4 His139 to Arg139, was significantly different between the two groups of smokers. These data indicate that the gene polymorphism for mEPHX is not associated with susceptibility to emphysema in the Japanese population. The discrepancy between the two studies may be explained either by racial difference or by the selection bias of subjects in the previous study, which examined those who had only mild to moderate emphysema with lung cancer or those who were clinically diagnosed as having chronic obstructive pulmonary disease.

This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

Emerging evidences have shown the utility of saliva for the detection of SARS-CoV-2 by PCR as alternative to nasopharyngeal swab (NPS). However, conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads between NPS and saliva in 42 COVID-19 patients. Viral loads were estimated by the cycle threshold (Ct) values. SARS-CoV-2 was detected in 34 (81%) using NPS with median Ct value of 27.4, and 38 (90%) using saliva with median Ct value of 28.9 (P = 0.79). Kendall’s W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.