Peptide hormones and risk for future cardiovascular events among prediabetics: a 20-year follow-up in the OPERA study

Abstract

Background: Prediabetes has proven to have many unfavourable impacts on the cardiovascular system.

Methods: The OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study included 1045 middle-aged subjects followed from the years 1990–1993 to 2014. The focus was on peptide hormones.

Results: Plasma resistin levels were higher among prediabetics (p?=?.001), particularly impaired glucose tolerance (IGT) (p?<?.001), but not impaired fasting glucose (IFG) patients than among normal glucose tolerance (NGT) or diabetes groups. Diabetics showed lower resistin levels than IGT subjects (p?<?.001). IGT or diabetes groups showed lower adiponectin and higher leptin levels compared to the NGT group (p?<?.001). The IFG group had the highest blood pressure and left ventricular mass index, even higher than the diabetic group. Diabetics had the highest, prediabetics (IFG?+?IGT) intermediate and NGT the lowest risk for CVD events during follow-up (p?<?.001). Among prediabetics, high plasma ghrelin was an independent predictor of CVD events (p?<?.05) in the Cox regression analysis although it did not significantly improve either classification or discrimination of the patients.

Conclusions: Among glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics. Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.

• KEY MESSAGE

• Among glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics.

• Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.

     

Chlamydia and chronic arthritis

Abstract

Certain bacterial infections have been demonstrated to be causative of reactive arthritis. The most common bacterial trigger of reactive arthritis is Chlamydia trachomatis. Chlamydia pneumoniae is another known cause, albeit far less frequently. Although Chlamydia-induced reactive arthritis will often spontaneously remit, approximately 30% of patients will develop a chronic course. Modern medicine has provided rather remarkable advances in our understanding of the chlamydiae, as these organisms relate to chronic arthritis and the delicate balance between host and pathogen. C. trachomatis and C. pneumoniae both have a remarkable ability to disseminate from the initial site of infection and establish persistently viable organisms in distant organ sites, namely the synovial tissue. How these persistent chlamydiae contribute to disease maintenance remains to be fully established, but recent data demonstrating that long-term combination antimicrobial treatment can not only ameliorate the symptoms but eradicate the persistent infection suggest that these chronically infecting chlamydiae are indeed a driving force behind the chronic inflammation. We are beginning to learn that this all appears possible even after an asymptomatic initial chlamydial infection. Both C. trachomatis and C. pneumoniae are a clear cause of chronic arthritis in the setting of reactive arthritis; the possibility remains that these same organisms are culpable in other forms of chronic arthritis as well.     

病毒感染对慢性阻塞性肺疾病患者Th1/Th2偏移状态的影响

目的 探讨病毒感染与慢性阻塞性肺疾病(COPD)的关系,及病毒感染对COPD患者Th1/Th2偏移状态的影响.方法 应用间接ELISA法时81例COPD急性加重期患者、25例稳定期患者和22例正常对照者的血清进行呼吸道合胞病毒(RSV)、单纯疱疹病毒-1型(HSV-1)、副流感病毒(PIV)、腺病毒(ADV)、巨细胞病毒(CMV)的特异性抗体IgM进行检测.同时测定外周血单个核细胞上清液中细胞因子INF-γ和IL-4水平.结果 急性加重期组IgM阳性28例(34.57%),稳定期组和对照组lgM阳性率均为0,差异有统计学意义(X2=12.16,P<0.01).急性加重期组INF-γ和IL-4分别为(242±43)ng/L和(42±9)ng/L,稳定期组分别为(198±32)ng/L和(56±11)ng/L,对照组分别为(90±18)ng/L和(141±24)ng/L,差异有统计学意义(F分别为26.03和114.69,P均<0.01).急性加重期IgM阳性组INF-γ和IL4分别为(278±54)ng/L和(39±8)ng/L,阴性组分别为(185±33)ng/L和(61±13)ng/L,差异有统计学意义(t值分别为2.65和2.82,P均<0.01).结论 病毒感染是COPD急性加重期的重要诱因,COPD患者存在向Th1极化的调控,且病毒感染加强了COPD患者的Th1优势.     

夜间低氧对慢性阻塞性肺疾病患者血清IL-6、IL-8的影响

目的:探讨慢性阻塞性肺疾病(COPD)患者夜间低氧与全身炎症反应的关系。方法:选择中度至极重度COPD患者70例,年龄45～74岁,平均(65.41±7.84)岁。按多导睡眠监测结果将研究对象分为低氧组和非低氧组,均行肺功能和多导睡眠监测、炎症指标检测。比较各组血清IL-6及IL-8的差异,分析炎症指标与睡眠呼吸参数的相关性。结果:睡眠低氧组27例,低氧率为38.57%,低氧组血清IL-6、IL-8分别为(14.34±2.76) ng/mL、(68.49±9.65) ng/mL,明显高于非低氧组的(11.79±1.85) ng/mL、(61.62±8.47) ng/mL(均P0.001)。经校正年龄、体质量指数后,IL-6与睡眠呼吸相关参数TS88正相关(r=0.651,P=0.041),与最低SaO_2和平均SaO_2负相关(r=-0.644,P=0.038和r=-0.780,P=0.018);IL-8与睡眠呼吸相关参数TS88正相关(r=0.627,P=0.039),与最低SaO_2和平均SaO_2负相关(r=-0.659,P=0.026和r=-0.732,P=0.014)。结论:中度至极重度COPD患者夜间低氧普遍存在,低氧组患者全身炎症反应明显增强,全身炎症反应与夜间低氧相关。     

Effect of Prolonged Treatment with Azithromycin, Clarithromycin, or Levofloxacin on Chlamydia pneumoniae in a Continuous-Infection Model

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1β, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.     

Circulating levels of interleukin-18 in patients with non-alcoholic fatty liver disease

Abstract

Background and aims. Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and diabetes mellitus. IL-18 is associated with obesity and metabolic syndrome. Our aim was to investigate the relationship of IL-18 with adiponectin and liver histology in subjects with NAFLD who had no additional disorder such as morbid obesity, diabetes mellitus and hypertension. Methods. Plasma levels of IL-18 and adiponectin were measured by ELISA in 96 male subjects with NAFLD [n = 65 for non-alcoholic steatohepatitis (NASH) and n = 31 for simple steatosis (SS)]. Results. IL-18 levels were not different between the two groups (p = 0.89). There was no significant association of IL-18 with adiponectin, insulin resistance and histopathological findings. Adiponectin was lower in the NASH group compared to the SS group (p = 0.02) and it was found to be negatively correlated with hepatic steatosis and fibrosis (r = ?0.442, p < 0.001 and r = ?0.292, p = 0.02, respectively). Conclusions. This study indicates that circulating IL-18 levels are not altered in male subjects with NAFLD. These results suggest that in the absence of metabolic risk factors, IL-18 per se may not be involved in the pathogenesis of NASH and SS.     

Management of bacterial infections in children with asthma

Respiratory viruses are the single most common causes of asthma exacerbations in children. Rhinovirus-induced wheezing is a risk factor for chronic asthma, but its mechanism has remained unknown. Human bocavirus is a common finding in wheezing children, but its role as a respiratory pathogen is still unclear. Mycoplasma pneumoniae may, like viruses, induce wheezing and asthma exacerbation. Chlamydia pneumoniae and, in recent studies, Chlamydia trachomatis, may not only induce asthma exacerbations but may also be involved in the pathogenesis of chronic asthma. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. This review summarizes current knowledge on the association between respiratory infections and asthma in children, with a special focus on the role of antibiotics in incipient asthma, asthma exacerbation and chronic stable asthma.     

Adipocytokine concentrations in children with different types of beta-thalassemia

Abstract

Background. Beta-thalassemia is an inherited blood disorder. It results from the impaired production of β-globin chains, leading to a relative excess of alpha-globin chains. Clinical severity separates this disease into three main subtypes: β- thalassemia major, β-thalassemia intermedia and β-thalassemia minor, the former two being clinically more significant. Inflammatory processes may play an important role in some of the complications of thalassemia. Adipose tissue is one of the most important endocrine and secretory organs that release adipocytokines like adiponectin, resistin and visfatin. Aim. The aim of our study was to analyze adipocytokine concentrations (adiponectin, resistin and visfatin) in different types of β-thalassemia patients and determine any possible correlations with disease severity. Methods. We recruited 29 patients who were transfusion-dependent β-thalassemia-major patients, 17 patients with β-thalassemia intermedia, 30 β-thalassemia minor patients. The control group consisted of 30 healthy children. Anthropometric measurements, complete blood count, biochemical parameters, serum concentrations of adiponectin, resistin, visfatin were performed for all subjects. Results. Resistin and visfatin concentrations were significantly higher in β-thalassemia minor patients than in controls. Adiponectin, resistin and visfatin concentrations were significantly higher in both β-thalassemia intermedia and major patients than in controls. The concentrations of adiponectin, resistin and visfatin were significantly higher in both β-thalassemia intermedia and major patients than in β-thalassemia minor patients. There was no significant difference between β-thalassemia intermedia and β-thalassemia major patients for adipocytokines concentrations. Conclusion. We speculate that these adipocytokines may play a role in the development of complications in β-thalassaemia.     

Adiponectin as a biomarker of systemic inflammatory response in smoker patients with stable and exacerbation phases of chronic obstructive pulmonary disease

Background and objective. Adiponectin is an adipose tissue‐derived specific protein that has a role in energy homeostasis, that has a protective role against the development of insulin resistance and atherosclerosis and that exhibits anti‐inflammatory properties. We investigated serum adiponectin as a biomarker of systemic inflammatory response and its relation with leptin, C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and nitric oxide (NO) in chronic obstructive pulmonary disease (COPD) patients. Material and methods. We studied 36 male patients with COPD (15 stable and 21 exacerbated) and 17 age and sex‐matched healthy subjects. The adiponectin and leptin levels were measured by enzyme‐linked immunosorbent assay. Serum CRP levels were measured using the nephelometric method. ESR was determined using the Westergren method and NO by the cadmium reduction method. Results. Adiponectin levels in COPD patients were significantly higher than those in control subjects (p<0.001), whereas there were no differences in leptin or NO levels. Serum levels of CRP, ESR and adiponectin were significantly higher in the exacerbated COPD patients compared to the stable group (p<0.001, p = 0.033 and p = 0.024, respectively), whereas the differences in leptin and NO levels were not significant. Serum levels of adiponectin were not correlated with FEV₁, FEV₁/FVC, dyspnoea score, BMI or other inflammatory parameters in the stable COPD group. CRP and ESR correlated negatively with FEV₁ in the stable COPD group. Conclusions. Adiponectin may be a marker of low‐grade systemic inflammatory response in COPD. A further rise in serum adiponectin in the exacerbation period denotes that this may also be a biomarker of the exacerbation phase as well as CRP and ESR.     

Comparison of complement fixation and microimmunofluorescence tests in respiratory infections caused by chlamydia and an evaluation of the serum amyloid a protein in chlamydial infections

We retrospectively analyzed serum samples for antibodies to chlamydia species using the micro-immunofluorescence (MIF) test from 72 patients previously tested by the clamydia complement fixation (CF) test, which is used to detect pulmonary psittacosis. Nineteen patients were positive for chlamydia with the CF test. Of these, 9 patients (47.4%) were also positive forC. psittaci infection, and 7 patients (36.8%) were positive forC. pneumoniae infection by the MIF test. Five (9.4%) and (11.3%) of the 53 CF-negative patients were positive for psittacosis andC. pneumoniae infection by the MIF test, respectively. Our results indicate that the serum of patients suspected of pulmonary psittacosis should be examined by the MIF test as well as CF in order to distinguish between infections caused byC. psittaci, C. pneumoniae andC. trachomatis, and to improve the sensitivity of serodiagnosis. Serum samples of all 7 patients positive by both CF and the MIF test forC. pneumoniae infection showed a diagnostic IgG antibody change toC. pneumoniae without IgM antibody changes, which suggested a primary infection. These results suggest that the diagnostic CF antibody response occasionally appears in reinfection, especially inC. pneumoniae infection. There was a positive correlation (r=0.858) between C-reactive protein and serum amyloid protein A, a sensitive acutephase serum reactant, over a wide range of concentrations in 19 patients with chlamydia respiratory infections.     

Echinacea purpurea along with zinc, selenium and vitamin C to alleviate exacerbations of chronic obstructive pulmonary disease: results from a randomized controlled trial

What is known and objective: Upper respiratory tract infections (URTI) frequently cause exacerbations of chronic‐obstructive pulmonary disease (COPD). Stimulation of the innate immune system may provide an early defence against such infections. The objective of this study was to determine whether Echinacea purpurea (EP) along with micronutrients may alleviate COPD exacerbations caused by acute URTI. Methods: This was a double‐blind, randomized, placebo‐controlled trial in COPD patients with acute URTI. Patients were given ciprofloxacin for 7 days and additionally one tablet per day of EP, of EP along with zinc, selenium and ascorbic acid (EP+), or of placebo until day 14. Serum levels of TNF α and interleukins 1β, 6 and 10 were measured before and after treatment. Until week 4 post‐end of treatment, all patients had to daily report on COPD symptoms in diaries. Results and Discussion: In total, 108 mostly male patients with a mean age of 65·8 years (40–81 years) were enrolled. Patients of the three treatment arms did not vary significantly in baseline characteristics. EP+, but not EP resulted in significantly less severe and shorter exacerbation episodes following URTI as compared with placebo suggesting a synergistic effect of Echinacea and micronutrients. Large variations in biomarkers in‐between and within groups were unrelated to treatment. Study medication was safe and well tolerated with overall 15 adverse events one of which was serious. Among those, sleeping disorders were most frequent and likely related to the underlying disease. What is new and Conclusion: The combination of EP, zinc, selenium and vitamin C may alleviate exacerbation symptoms caused by URTI in COPD. Further studies are warranted to investigate the interactions among Echinacea, zinc, selenium and vitamin C.     

Serum levels of leptin, adiponectin and resistin are interrelated and related to total antioxidant capacity, free fatty acids and phospholipids in early neonatal life

ObjectivesThe aims of this study were to determine interrelationships between serum leptin, adiponectin and resistin, insulin-like growth factor-1 (IGF-1), total antioxidant capacity (TAC), non-esterified fatty acids (NEFA) and phospholipids concentrations in infants.Design and methodsA cross-sectional study was conducted to assess serum levels of leptin, adiponectin, resistin, IGF-1, TAC, NEFA and phospholipids in 45 breast-fed infants enrolled at 4–30 days after birth.ResultsSerum leptin and adiponectin concentrations were positively correlated. Serum resistin concentrations were inversely correlated to serum leptin and adiponectin concentrations. Serum TAC was positively correlated to serum leptin and adiponectin, and inversely to serum resistin concentrations. Serum adiponectin concentrations were positively related to serum NEFA and phospholipid concentrations. Serum resistin concentrations were inversely related to serum NEFA, and phospholipid concentrations.ConclusionThese data show that circulatory levels of leptin, adiponectin and resistin are interrelated and they apparently interact with the anti-oxidant system of infants.     

Cytokines and statin therapy in chronic obstructive pulmonary disease patients

Abstract

Cytokines are biological response modifiers involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). This study investigated the potential use of cytokines as disease severity biomarkers in COPD patients and the possible effect of statin therapy on cytokine expression. Possible associations between cytokines, body mass index (BMI) and smoking have also been studied. Cytokines IFN-γ, IL-2, IL-12 p70, TNF-α, TNF-β, IL-4, IL-5, IL-6, IL-10, IL-1β and IL-8 were measured in the plasma of 100 clinically stable COPD patients using a fluorescent bead immunoassay on a flow cytometer. When patients were grouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage (A-D), no significant differences in cytokine concentrations were found (p?>?.05). Significantly decreased concentrations of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and TNF-α were found in COPD patients receiving statin therapy in comparison with COPD patients not receiving statin therapy (p?25) had decreased IL-2 (p=.038), IL-8 (p?=?.039) and IL-10 (p?=?.005) concentrations compared to normal BMI (20–25) patients. Current COPD smokers had increased concentrations of IL-5 (p?=?.037) compared to former COPD smokers. Hierarchical cluster analysis showed several patterns of measured cytokines in serum of patients with stable COPD. Statin therapy is associated with decreased expression of selected Th1 and Th2 cytokines in COPD, and this effect could be of relevance in COPD patients with increased cardiovascular risk. Concentrations of Th1 and Th2 cytokines in plasma cannot be used as biomarkers of disease severity or progression of COPD.     

Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation

Objective. Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase‐2 (matrix metalloproteinase‐8 (MMP‐8)) and gelatinase B (MMP‐9). We investigated the activity of NE and the levels of MMP‐8 and MMP‐9 in a longitudinal setting at and after COPD exacerbation using a non‐invasive technique, i.e. induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation. Material and methods. The study included healthy non‐smokers (n = 32), healthy smokers (n = 28), patients with stable COPD (n = 15), COPD patients with acute exacerbations (exa) (n = 10) and their recovery (n = 8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP‐8 levels by immunofluorometry and MMP‐9 levels by ELISA were analysed from induced sputum supernatants. Results. NE activity and the level of MMP‐8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p<0.0001; MMP‐8: p<0.001 and p<0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity). Conclusions. COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP‐8, which can be detected from the induced sputum supernatants of these COPD patients.     

Low prevalence of Chlamydia pneumoniae infections during the Mycoplasma pneumoniae epidemic season: Results of nationwide surveillance in Japan

ObjectiveChlamydia pneumoniae and Mycoplasma pneumoniae are both common causes of atypical pneumonia. We conducted an annual national survey of Japanese children to screen them for C. pneumoniae infections during the M. pneumoniae epidemic season.MethodsNasopharyngeal swab specimens were collected from children aged 0–15 years with suspected acute lower respiratory tract infection due to atypical pathogens, at 85 medical facilities in Japan from June 2008 to March 2018. Specimens were tested for infection using real-time polymerase chain reaction assays.ResultsOf 5002 specimens tested, 1822 (36.5%) were positive for M. pneumoniae alone, 42 (0.8%) were positive for C. pneumoniae alone, and 20 (0.4%) were positive for both organisms. In children with C. pneumoniae infection, the median C. pneumoniae DNA copy number was higher in those with single infections than in those with M. pneumoniae coinfection (p = 0.08); however it did not differ significantly according to whether the children had received antibiotics prior to sample collection (p = 0.34).ConclusionsThe prevalence of C. pneumoniae infection was substantially lower than that of M. pneumoniae infection during the study period. The change in prevalence of C. pneumoniae was not influenced by that of M. pneumoniae. Children with single C. pneumoniae infection are likely to have had C. pneumoniae infection, while those with coinfection are likely to have been C. pneumoniae carriers.     

Urinary tract infection during pregnancy affects the level of leptin,ghrelin and insulin in maternal and placental blood

Abstract

Aim. We examined ghrelin, leptin and insulin in maternal blood during normal pregnancy and pregnancy complicated by urinary tract infection (UTI), as well as in cord blood at labor. Methods. A total of 36 delivering women with history of UTI during the third trimester of pregnancy were enrolled in the study; 12 healthy pregnant women served as a control. Infection markers (CRP and procalcitonin) were determined in maternal blood during the course of UTI and at labor. Ghrelin, leptin and insulin were determined during labor in venous maternal and in umbilical cord blood. Results. We found negative correlation between infection markers in maternal blood during UTI, and level of tested hormones in cord blood, indicating potential risk of placental impairment due to energetic imbalance. We noted lower level of leptin in mothers with UTI and no change in leptin from umbilical blood comparing subjects with and without UTI. Low level of ghrelin was observed in maternal and cord blood when pregnancy was complicated by UTI. Insulin concentrations were high in mothers with UTI and low in their newborn's cord blood. Increased maternal insulin level could indicate peripheral insulin resistance caused by the infection. Conclusion. UTI during pregnancy affects the concentration of hormones responsible for regulating energetic homeostasis within the placenta.     

肺炎衣原体感染对慢性阻塞性肺病患者T淋巴细胞亚群的影响

目的:探讨肺炎衣原体(CP)感染对慢性阻塞性肺病(COPD)患者T淋巴细胞亚群的影响。方法:选择COPD急性加重期患者176例,正常对照组46例。采用微量免疫荧光试验检测血清CP抗体IgG、IgA、IgM,采用流式细胞仪测定两组的外周血CD3 、CD4 、CD8 T淋巴细胞。结果:观察组急性CP感染率为27.3%,慢性CP感染率为19.3%,与对照组比较有显著差异(P<0.01)。CD3 、CD4 细胞在各组间无差异,COPD患者中慢性CP感染组的CD8 细胞升高、CD4 /CD8 比值降低,较对照组有明显差异(P<0.01),而急性CP感染组和阴性组的CD8 细胞及CD4 /CD8 比值与对照组差异不明显。结论:CP感染是COPD急性加重的重要诱因,CP感染特别是慢性感染是引起COPD患者细胞免疫功能紊乱的重要原因,而这种细胞免疫功能的紊乱可能参与了COPD的发病。     

Chlamydia pneumoniae and its role in chronic obstructive pulmonary disease

The diverging of T-helper (Th) cells into predominantly Thl and Th2 subsets on the basis of their cytokine profiles has decisively improved our understanding of the pathogenesis of many chronic infectious diseases. Recent data suggest that the presence of interferon-γ and the subsequent suppression of interleukin-4 production leads to a Thl-type reponse that is required for the resolution of infections caused by intracellular pathogens. The ability of the macrophages to respond aggressively during early antigen contact seems to be one crucial factor in the development of an appropriate Th-cell response. Several host-related factors can affect macrophage function and the polarization of T-cell responses, ie the shift from a Thl response to a Th2 one, and thus dramatically deteriorate the resolution of infections caused by intracellular agents such as Chlamydia pneumoniae. Chronic C. pneumoniae infection has been associated with several common chronic diseases, quite recently with chronic obstructive pulmonary disease. Chronic C. pneumoniae infection may amplify smoking-associated inflammation in the bronchi and may be a contributory factor in the development of irreversible pathological changes.