Multicentre comparison of self-management in patients with COPD.

In patients with COPD, self-management plays an important role in disease management. Recently, self-management programmes have expanded patient education practices to include a variety of disease management techniques. We hypothesised that COPD patients have insufficient and/or different self-management needs according to institution. We compared information needs of patients between specialised clinics in Canada (SCC) and Japan and a hospital outpatient clinic in Japan (HCJ), all employing different self-management interventions. This cross-sectional study evaluated patients' information needs for disease management using the Lung Information Needs Questionnaire (LINQ). Furthermore, we assessed pulmonary function tests, modified Medical Research Council (mMRC) dyspnoea scale and frequencies of hospitalisations and emergency visits. The total number of patients was 183. Those attending SCC were younger (p=0.047), with lower forced expiratory volume in 1 s % predicted (p<0.0001), and scored higher on the mMRC dyspnoea scale. Total LINQ scores showed differences between institutions (p<0.0001). There was no difference for the smoking domain; however, SCC recorded significantly lower information needs for all other domains (p<0.02). No significant difference in emergency visits was seen between institutions, but HCJ recorded the highest rate of emergency visits, while SCC had significantly higher rates of hospitalisation (p=0.004). Differences were seen for frequency and duration of education between institutions. These results highlight the differences in information needs by institution and the importance of assessing individual needs. We believe, despite representing only one aspect of self-management, our findings reflect real-world circumstances, adding to the argument that self-management education should be structured, but flexible, to meet the changing needs of COPD patients.

Polysomnographic features of low arousal threshold in overlap syndrome involving obstructive sleep apnea and chronic obstructive pulmonary disease.

PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.

Gender Differences in Chronic Obstructive Pulmonary Disease Using the Lung Information Needs Questionnaire.

Aim: To investigate gender-related information needs in patients with chronic obstructive pulmonary disease (COPD) using the Lung Information Needs Questionnaire (LINQ). Design: Cross-sectional, prospective cohort study. Methods: Patients with COPD receiving standardized self-management education including information regarding disease knowledge, medications, avoidance of exacerbation, smoking cessation, exercise, and nutrition were included. Gender differences were assessed by pulmonary function tests, 6-minute walking test, modified Medical Research Council dyspnea scale, Mini-Mental State Examination, St. George's Respiratory Questionnaire, and LINQ. Results: A total of 122 patients were enrolled. Females displayed significantly higher information needs for total LINQ score (p < .001), avoidance of exacerbation (p < .03), and nutrition (p < .006). Significant correlations were seen between total LINQ score and gender (p = .001), forced expiratory volume in 1 second, % predicted (p = .003), and Mini-Mental State Examination (p = .002) for male patients. In females, modified Medical Research Council dyspnea scale was correlated with the total LINQ score (p = .04).

High affinity sugar ligands of C-type lectin receptor langerin.

BACKGROUND: Langerin, a C-type lectin receptor (CLR) expressed in a subset of dendritic cells (DCs), binds to glycan ligands for pathogen capture and clearance. Previous studies revealed that langerin has an unusual binding affinity toward 6-sulfated galactose (Gal), a structure primarily found in keratan sulfate (KS). However, details and biological outcomes of this interaction have not been characterized. Based on a recent discovery that the disaccharide L4, a KS component that contains 6-sulfo-Gal, exhibits anti-inflammatory activity in mouse lung, we hypothesized that L4-related compounds are useful tools for characterizing the langerin-ligand interactions and their therapeutic application. METHODS: We performed binding analysis between purified long and short forms of langerin and a series of KS disaccharide components. We also chemically synthesized oligomeric derivatives of L4 to develop a new high-affinity ligand of langerin. RESULTS: We show that the binding critically requires the 6-sulfation of Gal and that the long form of langerin displays higher affinity than the short form. The synthesized trimeric (also designated as triangle or Tri) and polymeric (pendant) L4 derivatives displayed over 1000-fold higher affinity toward langerin than monomeric L4. The pendant L4, but not the L4 monomer, was found to effectively transduce langerin signaling in a model cell system. CONCLUSIONS: L4 is a specific ligand for langerin. Oligomerization of L4 unit increased the affinity toward langerin. GENERAL SIGNIFICANCE: These results suggest that oligomeric L4 derivatives will be useful for clarifying the langerin functions and for the development of new glycan-based anti-inflammatory drugs.

Effectiveness of home-based exercise in older patients with advanced chronic obstructive pulmonary disease: A 3-year cohort study.

AIM: To determine whether home-based exercise can improve clinical outcomes in older patients with advanced chronic obstructive pulmonary disease using long-term oxygen therapy. METHODS: Information was provided to improve chronic obstructive pulmonary disease self-management before the onset of the present prospective 3-year cohort study. Patients selected either home-based exercise using a lower-limb cycle machine (ergo-bicycle; group E), or usual exercise (group U). To assess self-management, the Lung Information Needs Questionnaire was evaluated every 6 months. Clinical outcomes included the 6-min walk test, pulmonary function tests, the body mass index, airflow obstruction, dyspnea and exercise index, St. George's respiratory questionnaire, and the number of exacerbations and hospitalizations. RESULTS: A total of 136 patients (group E = 72; group U = 64), with a mean age of 74.2 years were enrolled. Total Lung Information Needs Questionnaire scores improved over 3 years for group E (P = 0.003). The distance of the 6-min walk test was well maintained in group E, but significantly decreased in group U (P < 0.001). The percentage of forced expiratory volume in 1 s at baseline was lower in group E (P = 0.016), but was maintained over 3 years, whereas a significant reduction was seen in group U (P = 0.001). The body mass index, airflow obstruction, dyspnea and exercise index significantly worsened in both groups over 3 years (group E: P = 0.011; group U: P < 0.001), whereas a significant decrease in the number of exacerbations was noted in group E (P = 0.009). CONCLUSIONS: Patients who undertook home-based exercise using an ergo-bicycle were able to maintain clinical outcomes including 6-min walk test distance and percentage of forced expiratory volume in 1 s predicted, and recorded fewer exacerbations over 3 years. Geriatr Gerontol Int 2018; 18: 42-49.

Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency.

BACKGROUND AND OBJECTIVE: The exacerbation-prone phenotype of COPD is particularly important, as exacerbations lead to poor quality of life and disease progression. We previously found that COPD patients who lack Siglec-14, a myeloid cell protein that recognizes bacteria and triggers inflammatory responses, are less prone to exacerbation. We hypothesized that the variations in other SIGLEC genes could also influence COPD exacerbation frequency, and investigated the association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of COPD. METHODS: We examined whether SIGLEC9 polymorphisms affect the frequency of COPD exacerbation in 135 subjects within our study population, and also analysed the correlation between the genotypes and the severity of airflow obstruction and emphysema in 362 Japanese smokers including 244 COPD patients. The association between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were also assessed in a Caucasian population of ECLIPSE study. The effects of these coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro assays. RESULTS: The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA) haplotype in SIGLEC9 was associated with higher frequency of exacerbations and the extent of emphysema in COPD. These results did not replicate in the ECLIPSE study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA haplotype produced more TNF-α than the one expressing the variant corresponding to the other major haplotype. CONCLUSION: The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema.

A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models.

Emphysema is a typical component of chronic obstructive pulmonary disease (COPD), a progressive and inflammatory airway disease. However, no effective treatment currently exists. Here, we show that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette smoke-exposed mice. To confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3--6]Galß1-4[SO3--6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and microcomputed tomography analyses revealed that, in the mouse elastase-induced emphysema model, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx, as well as the levels of inflammatory cytokines, tissue-degrading enzymes (matrix metalloproteinases), and myeloperoxidase in bronchoalveolar lavage fluid, suggesting that L4 suppressed inflammation in the lung. L4 consistently blocked the chemotactic migration of neutrophils in vitro. Moreover, in the case of the exacerbation model, L4 inhibited inflammatory cell accumulation to the same extent as that of dexamethasone. Taken together, L4 represents one of the potential glycan-based drugs for the treatment of COPD through its inhibitory action against inflammation.

[Management of older adults with COPD].

In older adults, the clinical condition of COPD is complicated and treatment often becomes difficult, because of existence of multimorbidity, such as nutritional deficiencies, thinness, sarcopenia, osteoporosis, cardiovascular disease, depression and cognitive impairment. Consideration based on each of coexistence is needed in the management of older adults with COPD. In end period of COPD, sleep disorder, depressive state and decline of ADL are often shown, in addition to the respiratory symptoms, such as dyspnea, cough and sputum. Financial strain for the nursing cost and medical equipment cost tend to become big year by year, utilization of social resources (i.e. application of respiratory disabilities and an insurance of the elderly care) is need to be considered.

The Neutrophil to Lymphocyte Ratio Is Related to Disease Severity and Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p<0.001 for all), while inversely correlated with airflow obstruction (p<0.001), body mass index (p<0.001), fat-free mass index (p=0.001), and the 6-minute walk distance (p<0.001). We obtained the NLR during exacerbation from 49 patients. The NLR was significantly higher at exacerbation compared to the stable state (p<0.001). Conclusion The NLR was associated with disease severity and exacerbation in COPD patients. Therefore, the usefulness of the NLR in COPD patients should be elucidated in clinical settings in future investigations.

Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling.

To date, a number of potential biomarkers for lung squamous cell cancer (SCC) have been identified; however, sensitive biomarkers are currently lacking to detect early stage SCC due to low sensitivity and specificity. In the present study, we compared the 7 serum proteomic profiles of 11 SCC patients, 7 chronic obstructive pulmonary disease (COPD) patients and 7 healthy smokers as controls to identify potential serum biomarkers associated with SCC and COPD. Two-dimensional difference gel electrophoresis (2D-DIGE) and mass-spectrometric analysis (MS) using an affinity column revealed two candidate proteins, haptoglobin (HP) and apolipoprotein 4, as biomarkers of SCC, and α-1-antichymotrypsin as a marker of COPD. The iTRAQ technique was also used to identify SCC-specific peptides. HP protein expression was significantly higher in SCC patients than in COPD patients. Furthermore, two HP protein peptides showed significantly higher serum levels in SCC patients than in COPD patients. We established novel polyclonal antibodies for the two HP peptides and subsequently a sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of these specific peptides in patient and control sera. The sensitivity of detection by ELISA of one HP peptide (HP216) was 70% of SCC patients, 40% of COPDs patients and 13% of healthy controls. We also measured CYFRA, a cytokeratin fragment clinically used as an SCC tumor marker, in all the 28 cases and found CYFRA was detected in only seven SCC cases. However, when the measurement of HP216 was combined with that of CYFRA, 100% (10 of 10 patients) of SCC cases were detected. Our proteomic profiling demonstrates that the SCC-specific HP peptide HP216 may potentially be used as a diagnostic biomarker for SCC.

Atrial and Ventricular Arrhythmia-Associated Factors in Stable Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Supraventricular and ventricular premature complexes (SVPC and VPC, respectively) are associated with chronic obstructive pulmonary disease (COPD) and with increased mortality in COPD patients. However, there are few reports on the causes of arrhythmia in COPD patients. OBJECTIVES: This study explores the associations between cardiopulmonary dysfunction and COPD by comparing patients with defined arrhythmias (>100 beats per 24 h) and those without, based on 24-hour electrocardiogram (ECG) recordings. METHODS: Patients with arrhythmia underwent a 24-hour ECG and subsequent pulmonary function tests, computed tomography, ECG, 6-min walk test (6MWT), and BODE (body mass index, airflow obstruction, modified Medical Research Council Dyspnoea Scale, exercise capacity) index calculation. RESULTS: Of 103 study patients (71 COPD patients and 32 at-risk patients), 36 had VPC, 45 had SVPC, 20 had both, and 42 had neither. The predicted post-bronchodilator forced expiratory volume in 1 s, the proportion of low-attenuation area on computed tomography, and BODE index values were significantly worse in the SVPC and VPC groups compared with the corresponding reference groups. Patients in the VPC group showed significantly increased right ventricular pressure and increased desaturation in the 6MWT compared with the reference group. In the multivariate analyses, bronchodilator use was a significant risk factor in the SVPC group, whereas in the VPC group, all parameters of the BODE index except for the dyspnoea score were identified as risk factors. CONCLUSIONS: Increased SVPC might be caused by bronchodilator use, whereas increased VPC is likely related to the peculiar pathophysiology of COPD.

Long-term effects of gastrectomy in patients with spirometry-defined COPD and patients at risk of COPD: a case-control study.

OBJECTIVE: Comorbidities are characteristic of COPD. However, little is known about the secondary manifestations of COPD in the gastrointestinal tract. Therefore, we aimed to explore the long-term effects of gastrectomy in patients with spirometry-defined COPD or those at risk of COPD. PARTICIPANTS: Subjects included 87 patients either with COPD or at risk of COPD (symptomatic) who underwent gastrectomy between December 2003 and October 2013 (group A), and 174 patients either with COPD or at risk of COPD, matched by age (±5 years), sex, and forced expiratory volume in 1 second (FEV1) as percentage of predicted (FEV1% predicted) (±5%) (group B). METHODS: All patients underwent routine blood chemistry and pulmonary function tests, arterial blood gas analysis, 6-minute walk test (6MWT), high-resolution chest computed tomography scans, and nutritional assessments. RESULTS: The mean duration postgastrectomy was 18.3±15.4 years. The mean FEV1 and FEV1% predicted were 2.07±0.76 L and 74.6±24.5%, respectively. Univariate analysis indicated that group A patients had significantly lower body mass index, fat-free mass index, and serum hemoglobin and albumin concentration (all P=0.00), and walked a significantly shorter distance in the 6MWT (P<0.05). Multivariate linear regression analysis for the distance in the 6MWT indicated that increased residual volume (RV) to total lung capacity (TLC) as percentage of predicted (%RV/TLC) alone was an independent and significant predictor of reduced distances in the 6MWT. CONCLUSION: We concluded that nutritional insufficiency in patients with COPD (or those at risk of COPD) who previously underwent gastrectomy might lead to hyperinflation and consequently, decreased exercise capacity.

Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease.

We previously reported that knockout mice for α1,6-fucosyltransferase (Fut8), which catalyzes the biosynthesis of core-fucose in N-glycans, develop emphysema and that Fut8 heterozygous knockout mice are more sensitive to cigarette smoke-induced emphysema than wild-type mice. Moreover, a lower FUT8 activity was found to be associated with a faster decline in lung function among chronic obstructive pulmonary disease (COPD) patients. These results led us to hypothesize that core-fucosylation levels in a glycoprotein could be used as a biomarker for COPD. We focused on a lung-specific glycoprotein, surfactant protein D (SP-D), which plays a role in immune responses and is present in the distal airways, alveoli, and blood circulation. The results of a glycomic analysis reported herein demonstrate the presence of a core-fucose in an N-glycan on enriched SP-D from pooled human sera. We developed an antibody-lectin enzyme immunoassay (EIA) for assessing fucosylation (core-fucose and α1,3/4 fucose) in COPD patients. The results indicate that fucosylation levels in serum SP-D are significantly higher in COPD patients than in non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings suggest that increased fucosylation levels in serum SP-D are associated with the development of COPD. BIOLOGICAL SIGNIFICANCE: It has been proposed that serum SP-D concentrations are predictive of COPD pathogenesis, but distinguishing between COPD patients and healthy individuals to establish a clear cut-off value is difficult because smoking status highly affects circulating SP-D levels. Herein, we focused on N-glycosylation in SP-D and examined whether or not N-glycosylation patterns in SP-D are associated with the pathogenesis of COPD. We performed an N-glycomic analysis of human serum SP-D and the results show that a core-fucose is present in its N-glycan. We also found that the N-glycosylation in serum SP-D was indeed altered in COPD, that is, fucosylation levels including core-fucosylation are significantly increased in COPD patients compared with non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings shed new light on the discovery and/or development of a useful biomarker based on glycosylation changes for diagnosing COPD. This article is part of a Special Issue entitled: HUPO 2014.

Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals. METHODS: We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test. RESULTS: Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV1% predicted] 75.0%). Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231-0.534, P=0.000 to P=0.042). Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV1% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= -0.482 to -0.377, P=0.000 to P=0.002). Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, ß=0.450, t=3.571, P=0.001), age (B=0.008, ß=0.352, t=2.789, P=0.009), and right ventricular systolic pressure (B=0.008, ß=0.280, t=2.202, P=0.035). CONCLUSION: Even in patients with stable chronic obstructive pulmonary disease, the serum troponin T concentration was controlled by at least three major factors, ie, systemic inflammation, advancing age, and right cardiac overload.

Proteomic and glycomic analyses of a lung-specific protein surfactant protein-D.

In order to verify the protein enriched from pooled human sera to be a lung-specific protein surfactant protein-D (SP-D), we performed peptide mass fingerprinting (PMF)-based protein identification. MASCOT search results of the obtained PMF unequivocally demonstrated that it is identical to human SP-D. Meanwhile, we performed MALDI-QIT-TOF mass spectrometry-based N-glycomic analysis of the recombinant human SP-D produced in murine myeloma cells. The obtained mass spectra of N-glycans from the recombinant SP-D demonstrated that the recombinant protein is almost exclusively modified with core-fucosylated N-glycans [1].

Senescence is involved in the pathogenesis of chronic obstructive pulmonary disease through effects on telomeres and the anti-aging molecule fibroblast growth factor 23.

AIM: Fibroblast growth factor 23 knockout mice develop premature aging and emphysema, indicating that dysregulation of the normal aging process is involved in the pathobiology of chronic obstructive pulmonary disease. Thus, we explored the association among a coding single-nucleotide polymorphism of fibroblast growth factor 23, its protein concentration in serum and telomere length in patients with chronic obstructive pulmonary disease. METHODS: The study involved 361 smokers; among whom, 244 were patients with chronic obstructive pulmonary disease. We genotyped a coding single-nucleotide polymorphism of fibroblast growth factor 23, rs7955866, and measured the telomere length of the peripheral blood cells. We also determined emphysema severity and airflow obstruction using computed tomography and pulmonary function tests, respectively. Furthermore, we analyzed the association between the disease phenotypes and fibroblast growth factor 23 genotypes or telomere length of peripheral blood leukocytes, as well as the association between the serum level of the studied protein and its genotypes. RESULTS: The mice with A alleles on rs7955866 showed severe upper lung emphysema (P = 0.008). The serum concentration of the tested protein was lower in the mice with A allele than in the G homozygotes (P = 0.004). Telomere shortening was associated with airflow obstruction (P = 0.009), but not with upper lung emphysema. CONCLUSIONS: A variation of fibroblast growth factor 23 with a reduced serum concentration appeared to promote emphysema formation. Telomere shortening in peripheral blood leukocytes was not associated with emphysema, but with airflow obstruction in chronic obstructive pulmonary disease through an independent mechanism.

Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema.

Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-ß1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-ß1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.

Association of serum interleukin-27 with the exacerbation of chronic obstructive pulmonary disease.

We have previously demonstrated that chronic obstructive pulmonary disease (COPD) patients who do not have Siglec-14 are less prone to exacerbation of the disease. Siglec-14 is a myeloid cell protein that recognizes bacteria and triggers inflammatory responses. Therefore, soluble mediators secreted by myeloid cells responding to Siglec-14 engagement could be involved in the pathogenesis of exacerbation and could potentially be utilized as biomarkers of exacerbation. To find out, we sought genes specifically induced in Siglec-14(+) myeloid cells and evaluated their utility as biomarkers of COPD exacerbation. Using DNA microarray, we compared gene expression levels in Siglec-14(+) and control myeloid cell lines stimulated with or without nontypeable Haemophilus influenzae to select genes that were specifically induced in Siglec-14(+) cells. The expressions of several cytokine and chemokine genes were specifically induced in Siglec-14(+) cells. The concentrations of seven gene products were analyzed by multiplex bead array assays in paired COPD patient sera (n = 39) collected during exacerbation and stable disease states. Those gene products that increased during exacerbation were further tested using an independent set (n = 32) of paired patient sera. Serum concentration of interleukin-27 (IL-27) was elevated during exacerbation (discovery set: P = 0.0472; verification set: P = 0.0428; combined: P = 0.0104; one-sided Wilcoxon matched-pairs signed-rank test), particularly in exacerbations accompanied with sputum purulence and in exacerbations lasting more than a week. We concluded that IL-27 might be mechanistically involved in the exacerbation of COPD and could potentially serve as a systemic biomarker of exacerbation.

Association of group component genetic variations in COPD and COPD exacerbation in a Japanese population.

BACKGROUND AND OBJECTIVE: Vitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation-prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population. METHODS: We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity. RESULTS: Subjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927). CONCLUSIONS: GC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression.

Predictors of chronic obstructive pulmonary disease exacerbations.

PURPOSE OF REVIEW: A frequent-exacerbation phenotype of chronic obstructive pulmonary disease (COPD) exists that is independent of disease severity. Establishment of methods to predict 'frequent exacerbators' is critical. The purpose of this review is to critically assess the recent literature regarding predicting COPD exacerbations, and to provide recommendations for future research. RECENT FINDINGS: Although there are many studies in which inflammatory biomarkers have been used in an attempt to predict future exacerbations, it is likely that these biomarkers represent a consequence rather than the cause. Genetic predictors are involved in causal pathways. Thus, genetics should be investigated in order to understand the exacerbation mechanism and to develop new therapeutic approaches. Some single nucleotide-type genetic polymorphisms are associated with exacerbations, and the individuals with genotypes protective against infection are less susceptible to exacerbations. In contrast, we reported that loss of Siglec-14, a lectin likely involved in host defense, was associated with a reduced COPD exacerbation risk. SUMMARY: We should take into consideration that a protein involved in host defense such as Siglec-14, that could also trigger exaggerated response, might also generate unwanted local and systemic inflammation, which could be detrimental to a host and could generate COPD with a frequent-exacerbation phenotype, its progression, and its comorbidities.