Control of chronic obstructive pulmonary disease in urban populations: findings from a cross-sectional prevalence survey in Shenzhen, China.

The prevalence of chronic obstructive pulmonary disease (COPD) among urban populations is generally lower than rural residents, but the disease burden is still high. We conducted a cross-sectional prevalence survey of COPD among residents aged ≥40 years in an emerging city Shenzhen, China from September 2018 to June 2019. Through multi-stage stratified random sampling, a total of 4157 eligible participants were invited to complete a questionnaire and to take the spirometry test; 3591 with available data were enrolled in the final analysis. Individuals were diagnosed with COPD if the post-bronchodilator FEV1/FVC ratio was less than 0.7. The estimated standardized prevalence of COPD among residents over 40 years old in Shenzhen was 5.92% (95% confidential intervals [CI] 4.05-8.34). Risk factors for COPD included elder age (adjusted odds ratio 1.206, 95% CI 1.120-1.299 per 10-year increase), smoking over 20 pack-years (1.968, 1.367-2.832), history of chronic bronchitis (1.733, 1.036-2.900) or asthma (4.920, 2.425-9.982), and exposure to higher annual minimum concentrations of ambient SO2 (1.156, 1.053-1.270 per 1-µg/m3 increase). Among 280 spirometry-diagnosed patients, most (221, 78.93%) patients were classified as mild COPD (GOLD stage I). This survey found that the prevalence of COPD in Shenzhen is low and most patients had mild symptoms, thus recommended screening using spirometry in primary health care to detect early-stage COPD. Increased risk from the exposure to air pollutants also indicated the urgent need for environmental improvement in city settings.

Presynaptic low- and high-affinity kainate receptors in nociceptive spinal afferents.

Presynaptic ionotropic glutamate receptors are increasingly attributed a role in the modulation of sensory input at the first synapse of dorsal root ganglion (DRG) neurons in the spinal dorsal horn. Central terminals of DRG neurons express AMPA and NMDA receptors whose activation modulates the release of glutamate, the main transmitter at these synapses. Previous work, with an antibody that recognizes all low-affinity kainate receptor subunits (GluR5, 6, 7), provided microscopic evidence of presynaptic kainate receptors in unidentified primary afferent terminals in superficial laminae of the spinal dorsal horn (Hwang SJ, Pagliardini S, Rustioni A, Valtschanoff JG. Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J Comp Neurol 2001; 436: pp. 275-289). We show here that, although all such subunits may be expressed in these terminals, GluR5 is the subunit most readily detectable at presynaptic sites in sections processed for immunocytochemistry. We also show that the high-affinity kainate receptor subunits KA1 and KA2 are expressed in central terminals of DRG neurons and are co-expressed with low-affinity receptor subunits in the same terminals. Quantitative data show that kainate-expressing DRG neurons are about six times more likely to express the P2X(3) subunit of the purinergic receptor than to express substance P. Thus, nociceptive afferents that express presynaptic kainate receptors are predominantly non-peptidergic, suggesting a role for these receptors in the modulation of neuropathic rather than inflammatory pain.

Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn.

Ionotropic glutamate receptors (IGR), including NMDA, AMPA, and kainate receptors, are expressed in terminals with varied morphology in the superficial laminae (I-III) of the dorsal horn of the spinal cord. Some of these terminals can be identified as endings of primary afferents, whereas others establish symmetric synapses, suggesting that they may be gamma-aminobutyric acid (GABA)-ergic. In the present study, we used confocal and electron microscopy of double immunostaining for GAD65, a marker for GABAergic terminals, and for subunits of IGRs to test directly whether IGRs are expressed in GABAergic terminals in laminae I-III of the dorsal horn. Although colocalization is hard to detect with confocal microscopy, electron microscopy reveals a substantial number of terminals immunoreactive for GAD65 also stained for IGRs. Among all GAD65-immunoreactive terminals counted, 37% express the NMDA receptor subunit NR1; 28% are immunopositive using an antibody for the GluR2/4 subunits of the AMPA receptor; and 20-35% are immunopositive using antibodies for the kainate receptor subunits GluR5, GluR6/7, KA1, or KA2. Terminals immunoreactive for IGR subunits and GAD65 establish symmetric synapses onto dendrites and perikarya and can be presynaptic to primary afferent terminals within both type 1 and type 2 synaptic glomeruli. Activation of presynaptic IGR may reduce neurotransmitter release. As autoreceptors in terminals of Adelta and C afferent fibers in laminae I-III, presynaptic IGRs may play a role in inhibiting nociception. As heteroreceptors in GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may have an opposite role and even contribute to central sensitization and hyperalgesia.

Primary afferent terminals that express presynaptic NR1 in rats are mainly from myelinated, mechanosensitive fibers.

Presynaptic N-methyl-D-aspartate (NMDA) receptors in terminals of primary afferents to spinal cord of rats were first reported by Liu et al. (1994; Proc. Natl. Acad. Sci. USA 91:8383-8387) and were proposed to modulate nociceptive input (Liu et al. [1997] Nature 386:721-724). We previously demonstrated kainate and AMPA receptors in numerous primary afferent terminals in the spinal cord fixed with diluted paraformaldehyde and no glutaraldehyde. Therefore, we reinvestigated the occurrence of presynaptic NMDAR1 (NR1) with this fixation protocol. With confocal microscopy, numerous immunofluorescent puncta were double-stained for NR1 and the presynaptic marker synaptophysin throughout the spinal gray. NR1-immunostained puncta costained more frequently with a tracer that labels myelinated afferents (cholera toxin subunit B; CTB) than with a tracer that labels non-peptidergic unmyelinated afferents (Griffonia simplicifolia isolectin B4; IB4). Virtually no double staining was found for NR1 and calcitonin gene-related peptide (CGRP), which labels somatic peptidergic primary afferents. In the gracile nucleus, virtually all puncta labeled for CTB appeared immunopositive for NR1. At the electron microscopic level, most immunopositive terminals in spinal cord and gracile nucleus displayed morphological characteristics of endings of myelinated primary afferents. NR1 was presynaptic in 60-65% of all synapses in which it was expressed pre- or postsynaptically, or both, in spinal laminae I-IV. Estimates for the gracile nucleus were higher (80%). No presynaptic NR1 was found in the ventroposterior thalamus. Because of the relative sparsity of presynaptic NR1 in terminals in laminae I and IIo and in terminals of peptidergic unmyelinated afferents, it is suggested that presynaptic NMDA receptors play a more significant role in modulation of mechanosensitive, innocuous input than in nociception.

Primary afferent terminals in spinal cord express presynaptic AMPA receptors.

Larger dorsal root ganglion neurons are stained by an antibody for the C terminus of glutamate receptor subunit 2 (GluR2) and GluR3 (GluR2/3) rather than by an antibody for GluR4. In dorsal roots, anti-GluR2/3 stains predominantly myelinated fibers; anti-GluR4 or anti-GluR2/4 stains predominantly unmyelinated fibers. In the dorsal horn, puncta immunopositive for synaptophysin and GluR2/3 are predominantly in laminas III and IV, whereas puncta immunopositive for synaptophysin and GluR4 or GluR2/4 are predominantly in laminas I and II. Puncta immunopositive for GluR2/3 costain with the B subunit of cholera toxin, whereas puncta immunopositive for GluR2/4 costain with isolectin B4 after injections of these tracers in the sciatic nerve. No puncta costain with calcitonin gene-related peptide and AMPA receptor subunits. Electron microscopy indicates that AMPA receptor-immunopositive terminals are more numerous than suggested by confocal microscopy. Of all synapses in which immunostaining is presynaptic, postsynaptic, or both, the percentage of presynaptic immunostain is approximately 70% with anti-GluR4 or anti-GluR2/4 (in laminas I-III), 25-30% with anti-GluR2/3 (in laminas III and IV), and 5% with anti-GluR2 (in laminas I-III). Because of fixation constraints, the types of immunostained terminals could be identified only on the basis of morphological characteristics. Many terminals immunostained for GluR2/3, GluR4, or GluR2/4 have morphological features of endings of primary afferents. Terminals with morphological characteristics of presumed GABAergic terminals are also immunostained with anti-GluR2/4 and anti-GluR4 in laminas I and II and with anti-GluR2/3 in laminas III and IV. The conspicuous and selective expression of presynaptic AMPA receptor subunits may contribute to the characteristic physiological profile of different classes of primary afferents and suggests an important mechanism for the modulation of transmitter release by terminals of both myelinated and unmyelinated primary afferents.

Two major distinct subpopulations of neurokinin-3 receptor-expressing neurons in the superficial dorsal horn of the rat spinal cord.

This study was designed to provide evidence for elucidating the mechanisms of neurokinin-3 receptor (NK3) in spinal pain modulation. First, colocalization of NK3 with the micro -opioid receptor (MOR1) was studied in the spinal dorsal horn of the rat. Confocal microscopy showed that about 44% of NK3-expressing neurons in laminae I and II were immunoreactive for MOR1, which corresponded to about 93% of the total population of MOR1-containing neurons in these laminae. Second, the relationship between NK3/MOR1-coexpressing neurons and those that express nitric oxide synthase (NOS) was examined by using a triple immunofluorescent staining method. About 37% of NK3-immunoreactive neurons were also NOS-immunoreactive, which constituted about 82% of NOS-immunoreacitve neurons in the superficial laminae. However, no triple-labelled neurons were detected. The present results indicate that there are two major distinct subpopulations of NK3-expressing neurons in the superficial dorsal horn, which suggests that the involvement of NK3 receptor in spinal nociception could be mediated by two distinct mechanisms, i.e. opioid and nitric oxide.