Infrequent Exacerbators Research Articles

Pro/Con: A unified conclusion-Inhaled corticosteroids for chronic obstructive pulmonary disease

ICS are like any other drug: they have benefits and they have risks.6,7 In the right patient, often the patient with frequent exacerbations and severe uncontrolled symptoms, an inhaler regimen, including dual long-acting bronchodilators and an ICS may be the right choice. For the patient with infrequent exacerbations, low symptom burden, and recent pneumonia that caused hospitalization, an inhaler regimen that contains an ICS may bring more risk than benefit. In addition, analysis of recent data, including the WISDOM8 trial, has provided evidence that ICS may be most beneficial in the immediate postexacerbation period. Further, ICS may be safely discontinued in patients with few exacerbations and stable symptoms.9 As with any long-term medication, a nuanced risk-benefit calculation by the prescribing physician and informed discussion with the patient are ultimately the best ways to balance the use of ICS that have benefits in some patients and risks in others.

Factors influencing decline in quality of life in smokers without airflow obstruction: The COPDGene study.

Current and former smokers with normal spirometry and with Preserved Ratio Impaired Spirometry (PRISm) experience respiratory events similar to chronic obstructive pulmonary disease (COPD) exacerbations. Exacerbations significantly reduce quality of life (QoL) in COPD patients however the effect of respiratory exacerbations on QoL in these groups is unknown. We hypothesized that exacerbations and change in exacerbation status would predict QoL decline among normal spirometry and PRISm participants in COPDGene. COPDGene is a multicenter, longitudinal study in the U.S. designed to identify genetic determinants of COPD. We enrolled study subjects in Phase 1 of COPDGene and performed multivariable logistic regression models to determine independent predictors of decline in quality of life [>4 points on the St George's Respiratory Questionnaire (SGRQ)]. Separate analyses were performed for current and former smokers with normal spirometry and PRISm. Frequent exacerbator status was defined by > 2 moderate or >1 severe exacerbations in the year prior to the baseline and year 5 follow-up visits. Independent predictors of QoL deterioration included current smoking, higher exacerbation frequency, and a change from infrequent to frequent exacerbation status (REF: infrequent to infrequent exacerbation status) in both groups [PRISm (OR = 3.15,95%CI, 1.67-5.94), normal spirometry (OR = 4.72,95%CI, 3.25-6.86)]. A change from frequent to infrequent exacerbation status did not lower the odds of QoL decline in either cohort. Continued smoking and the onset of frequent exacerbations were predictors of QoL decline in smokers with normal spirometry and PRISm. Further studies are needed to identify modifiable factors associated with decline in QoL in smokers.

Antiviral immunity is impaired in COPD patients with frequent exacerbations.

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.

Incidence of type II diabetes in chronic obstructive pulmonary disease: a nested case\u2013control study

We investigated the incidence of type II diabetes mellitus (T2DM) among people with COPD and whether exposure to inhaled corticosteroid (ICS) and exacerbation status was associated with T2DM. This descriptive cohort study used primary care data from the Clinical Practice Research Datalink (CPRD). The patient cohort included people with a diagnosis of COPD and previous smoking history registered at a CPRD practice between January 2010 and December 2016. We determined incidence rates by age, gender and deprivation. Using a nested case–control design—where cases and controls are drawn from the cohort population—we matched 1:5 with patients by age, gender and GP practice and estimated odds of T2DM using logistic regression (adjusting for smoking status, deprivation, BMI, hypertension, coronary heart disease and heart failure). We identified 220,971 COPD patients; mean age at COPD diagnosis was 66 years (SD 12) and 54% were male. The incidence rate of T2DM in COPD patients was 1.26 per 100 patient years (95% CI: 1.24–1.28) and was higher among men (1.32 vs 1.18 among women). The adjusted odds ratio for T2DM was 1.47 (95% CI: 1.36–1.60) among frequent exacerbators (≥2 treated exacerbations per year) compared to infrequent exacerbators and the odds ratio for patients receiving high-dose ICS (>800 mcg budesonide equivalent dose) was 1.73 (95% CI 1.65–1.82) compared to patients receiving no ICS therapy. Incidence of T2DM among COPD patients is high and exposure to ICS and frequent exacerbations are associated with a higher risk of T2DM among patients with COPD.

Chronic obstructive pulmonary disease upper airway microbiota alpha diversity is associated with exacerbation phenotype: a case-control observational study

BackgroundChronic obstructive pulmonary disease (COPD) frequent exacerbators (FE) suffer increased morbidity and mortality compared to infrequent exacerbators (IE). The association between the oral and sputum microbiota and exacerbation phenotype is not well defined. The objective of this study was to determine key features that differentiate the oral and sputum microbiota of FEs from the microbiota of IEs during periods of clinical stability.MethodsWe recruited 11 FE and 11 IE who had not used antibiotics or systemic corticosteroids in the last 1 month. Subjects provided oral wash and sputum samples, which underwent 16S V4 MiSeq sequencing and qPCR of 16S rRNA. Data were analyzed using Dada2 and R.ResultsFE and IE were similar in terms of age, FEV1 percent predicted (FEV1pp), pack-years of tobacco exposure, and St. George’s Respiratory Questionnaire score. 16S copy numbers were significantly greater in sputum vs. oral wash (p = 0.01), but phenotype was not associated with copy number. Shannon diversity was significantly greater in oral samples compared to sputum (p = 0.001), and IE samples were more diverse than FE samples (p < 0.001). Sputum samples from FE had more Haemophilus and Moraxella compared to IE sputum samples, due to dominance of these COPD-associated taxa in three FE sputum samples. Amplicon sequencing variant (ASV)-level analysis of sputum samples revealed one ASV (Actinomyces) was significantly more abundant in IE vs. FE sputum (padj = 0.048, Wilcoxon rank-sum test), and this persisted after controlling for FEV1pp. Principal coordinate analysis using Bray-Curtis distance with PERMANOVA analyses demonstrated clustering by anatomic site, phenotype, inhaled corticosteroid use, current tobacco use, COPD severity, and last professional dental cleaning.ConclusionsFE have less diverse oral and sputum microbiota than IE. Actinomyces was significantly more abundant in IE sputum than FE sputum. The oral and sputum microbiota of COPD subjects cluster based on multiple clinical factors, including exacerbation phenotype. Even during periods of clinical stability, the frequent exacerbator phenotype is associated with decreased alpha diversity, beta-diversity clustering, and changes in taxonomic abundance.

Identification of proteomic signatures associated with COPD frequent exacerbators

AimsAcute exacerbation is a major event that alters the natural course of chronic obstructive pulmonary disease (COPD), and recurrent exacerbation results in worse clinical outcomes and greater economic consequences. While some patients suffer frequent exacerbations, others experience no exacerbations; this study was designed to detect proteins that were differentially abundant in COPD frequent exacerbators and assess whether those expression profiles are unique among COPD patients. Main methodsTandem mass tag labeled quantitative proteomics combined with two-dimensional liquid chromatography-tandem mass spectrometry was used to detect the changes in the lung proteome in COPD frequent exacerbators and infrequent exacerbators. A series of bioinformatics analyses were performed to screen potential signatures of COPD frequent exacerbations. The accuracy of proteomic results was further verified by western blot studies. Key findingsCompared with infrequent exacerbators, 23 proteins in the lung tissues from frequent exacerbators showed significant degrees of differential expression; combined bioinformatics analyses of proteome indicated that the immune network for IgA production and the phenylalanine metabolism pathway were associated with frequent exacerbations. The Western blot analysis confirmed the expression pattern of three significantly regulated proteins (HLA-DQA1, pIgR and biglycan). SignificanceThese findings indicate that immune response might play a key role in the pathophysiological mechanisms of COPD frequent exacerbations. Our results make a crucial contribution to the search for a comprehensive understanding of potential pathophysiological mechanisms associated with the frequent exacerbations of COPD, and might provide guidance for treating frequent exacerbations.

Carotid intima-media thickness in chronic obstructive pulmonary disease and survival: A multicenter prospective study.

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Carotid intima-media thickness (CIMT) is a noninvasive method assessing atherosclerosis. It was aimed to determine relationship and survival between COPD and CIMT. CIMT was measured using Doppler ultrasound (USG) in 668 stable COPD patients at 24 centers. Patients were followed-up for 2 years. There were 610 patients who completed the study. There were 200 patients CIMT with <0.78 mm (group 1), and 410 with CIMT≥0.78 mm (group 2). There was a significant difference at the parameters of age, gender, smoking load, biomass exposure, GOLD groups and degree of airway obstruction (FEV1) between groups 1 and 2. Our results revealed positive correlations between mean CIMT and age, smoking load (pack-years), biomass exposure (years), exacerbation rate (last year), duration of hypertension (years) and cholesterol level; negative correlations between CIMT and FEV1 (P<0.05). According to logistic regression model, compared with group A, risk of CIMT increase was 2.2-fold in group B, 9.7-fold in group C and 4.4-fold in group D (P<0.05). Risk of CIMT increase was also related with cholesterol level (P<0.05). Compared with infrequent exacerbation, it was 2.8-fold in the patients with frequent exacerbation (P<0.05). The mean survival time was slightly higher in group 1, but not significant (23.9 vs 21.8 months) (P>0.05). This study is the first regarding CIMT with combined GOLD assessment groups. It has revealed important findings supporting the increase in atherosclerosis risk in COPD patients. We recommend Doppler USG of the carotid artery in COPD patients at severe stages.

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort.

The association between exacerbation aetiology and exacerbation frequency is poorly understood.We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years.The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p<0.01). This was not seen with other infection types or eosinophilic inflammation.Analysis of the same cohort over 2 years showed, for the first time, that changes in yearly COPD exacerbation rate may be associated with variations in H. influenzae colonisation.

Hypertension: A trigger or a consequence of exacerbations in COPD?

Hypertension is one of the most common diseases in the world, affecting 30–40% of the adult population. It is commonly associated with other comorbidities such as chronic obstructive pulmonary disease (COPD) which may influence the course of the disease. Besides, airflow limitation in COPD is a predictor of future risks of hypertension and cardiovascular events. In fact, COPD is now understood as a systemic inflammatory disease, with a focus of inflammation on the lungs. Assess the prevalence of hypertension in COPD patients. It is a randomized prospective study including 43 out-patient, aged from 50 to 92 years, affected with COPD. Each patient was subjected for 12-lead ECG, 24-hour Holter for arrhythmia detection and two-dimensional echocardiography. We compared a group G1 of patients with frequent exacerbations of COPD ( n = 23) to a group G2 of patients with infrequent exacerbations of COPD ( n = 20). The mean of age was 71 years in G1 vs. 65 years in G2. Also, a high significant difference was seen on comparing the mean of duration of COPD (5.57 years in G1 vs. 3 years in G2) ( P = 0.02). Half of the patients of G1 had associated comorbidities vs. 12% in G2 ( P = 0.01). From which hypertension accounted for 12% in G1 vs. 5% in G2 ( P = 0.01). In total, 18% presented with ischemic cardiovascular disease in G1 vs. 6% in G2. Besides, 24% of our patients had diabetes mellitus in G1 vs. 1% in G2. Most of the patients of G1 were asymptomatic (60% vs. 20% in G2). Six percent of the patients presented with dyspnea in G1 vs. 5% in G2. While 14% of our patients complained of chest pain vs. 5% in G2. There was a significant difference on comparing the mean of PaO2 (56 mmHg in G1 vs. 65 mmHg in G2) ( P = 0.015). In our study, the hypertension was significantly more common in the group of patients with frequent exacerbations of COPD underlying a pathophysiological link between COPD and hypertension which may be explained by an endothelial dysfunction.

The Chronic Obstructive Pulmonary Disease Frequent Exacerbator Phenotype Is Associated with Decreased Upper Airway Microbiota α Diversity

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD frequent exacerbators (FEs) suffer increased morbidity and mortality compared with infrequent exacerbators (IEs). Exace...

Body composition in patients with chronic obstructive pulmonary disease

The aim of this study was to investigate body composition in patients with COPD using two methods, Quételet index and bioelectrical impedance analysis (BIA), and to compare their diagnostic values.Methods. The study included 198 patients with COPD admitted to the Territorial Teaching hospital No.2, and 28 healthy volunteers. According to COPD severity, patients were divided into 4 groups; healthy volunteers (n = 28) were included in the control group. All groups were matched for sex and age. Anthropometry with body mass index (BMI) calculation and BIA were done in all participants.Results. The lowest average BMI was found in patients with severe and very severe COPD. Patients with infrequent exacerbations without decreased BMI had reduction in fat-free mass (FFM) in 12.3% (n = 25); 14.1% patients (n = 28) had increased body fat mass and decreased FFM. According to BIA results, reduction of FFM was seen significantly more often than reduction of BMI (57.6% vs 30%; χ2= 58.71; p = 0.03). BIA parameters describing muscle tissue were significantly related to the severity of bronchial obstruction (FEV1).Conclusion. Investigation of body composition using BIA method should be used as a tool for comprehensive examination of COPD patients, for personalized choice of treatment and in rehabilitation programs.

Analysis of clinical features and inflammatory factors in induced sputum in common phenotypes of COPD with frequent exacerbations

Objective To compare the clinical characteristics of chronic bronchitis (CB), emphysema (EM), asthma - chronic obstructive pulmonary disease overlapping syndrome (ACOS) with frequent exacerbations (FE) or infrequent exacerbations (iFE)and induced sputum inflammatory cells and the heterogeneity of the transmitter. Methods Ninety-one cases of chronic obstructive pulmonary disease(COPD)with acute exacerbation were divided into CB, EM or ACOS phenotype, among which 44 were frequent, and 47 were non frequent.The clinical data, induced sputum inflammatory cells, interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin(IL)-4, IL-13 were analyzed. Results The FEV1% was (47±13.1)%, significantly lower than that of non frequent episodes ((56.2±10.2)%), and the difference was statistically significant(P=0.049). The FEV1/FVC% was (54.3±9.3)%, significantly lower than that of non frequent episodes (60.1±7.3)%, and there was a significant difference between them (P=0.001). The proportion of patients with GOLD III and IV, the percentage of neutrophils in induced sputum, tumor necrosis factor -α(TNF-α) and interferon -γin the patients with frequent episodes were significantly higher than those with non frequent episodes (P<0.05). Among them, FEV1/FVC% and TNF-αwere independent risk factors for COPD patients (P=0.032, 0.021). The FEV1% of patients with CB phenotypic frequent episodes were (47.9±14.9)%, significantly lower than that of non frequent episodes ((57.2±10.9)% )(P=0.000), and FEV1/FVC% was (53.4±9.5)% in patients with CB frequent episodes, significantly lower than that of non frequent episodes ((60.3±6.9)%), and the difference was statistically significant (P=0.022), while the level of N%, TNF-α in induced sputum were significantly higher in CB phenotype subjects with FE than those in subjects with iFE(P<0.01). Patients with frequent episodes of emphysema had longer duration of disease (P<0.05), lower FEV1% and FEV1/FVC%(P<0.05), the proportion of GOLD III patients and the induced sputum TNF-αwere higher, but there was no significant difference in the number and proportion of phlegm inflammatory cells, interferon -γ, interleukin 4 and interleukin 3.The level of GOLD III and the IL-13 level of induced sputum in patients with frequent ACOS phenotype were significantly higher than those in patients with non frequent episodes (P<0.05). Conclusion The lung function, the severity of the disease, the course of the disease, and the percentage of sputum neutrophils, tumor necrosis factor -α, or interleukin 13 are helpful in diagnosing patients with high risk of frequent episodes. Key words: Chronic obstructive pulmonary disease; chronic bronchitis; emphysema; asthma-COPD overlap syndrome

Longitudinal trajectories of asthma exacerbations from infancy to school age.

IntroductionPrevious studies which used data-driven methodologies have reported the existence of an exacerbation-prone asthma subtype, which is independent of asthma severity. However, longitudinal patterns of asthma exacerbations during childhood have not been studied.&#x0D; Objectives and ApproachWe sought to investigate whether there are distinct longitudinal trajectories of asthma exacerbations from infancy to school-age that could facilitate better understanding of the heterogeneity of asthma syndrome.&#x0D; We used longitudinal k-means modelling (an unsupervised data-driven method), to analyse linked primary care data from 916 participants in a population-based birth cohort study (Manchester Asthma and Allergy Study), to ascertain clusters of children with similar trajectories of asthma exacerbations during childhood (n=160). We tested the validity of these clusters in relation to lung function, airway hyperreactivity and inflammation, allergic sensitisation, and the use of asthma medication.&#x0D; ResultsA two-cluster model provided the optimal solution for our data set. Based on the pattern of exacerbations from infancy to age 8 years, we assigned the clusters as: “Early-onset frequent exacerbations (FE)” (n=10) and “Infrequent exacerbations (IE)” (n=150). Shorter duration of breastfeeding was the strongest risk factor for FE (median weeks 0 (IQR: 0-1.75) vs IE, median weeks 6 (IQR: 0-20), p&lt;0.001). Children in the FE cluster were more likely to exhibit persistent wheeze (90% vs 47%, p=0.03) and have poorer lung function, more airway hyperreactivity, and more airway inflammation throughout childhood (Table 1). In a post-hoc analysis, when we compared children in the exacerbation clusters with those who have wheezed only (n=389), and those that wheezed but had no exacerbations (n=338), other early life risk factors such as atopic sensitisation (IE - RR: 3.2 (95%CI: 2.1-5.1), p&lt;0.001) (FE - RR: 10.9 (95%CI: 2.1-57.7), p=0.004), exposure to tobacco smoke at birth (FE - RR: 2.8 (95%CI: 1.3-6.3) ,p=0.02), position in sibship (IE - RR: 1.5 (95%CI: 1.0-2.3), p=0.03), and day care attendance (IE - RR:0.6 (95%CI: 0.4-0.9), p=0.01) were significantly associated with exacerbations.&#x0D; Conclusion/ImplicationsWe have identified two distinct patterns of asthma exacerbations during childhood with different outcomes, early-life risk factors, and lung function when compared to children who wheeze, but have no exacerbations. These results indicate that exacerbations represent an independent susceptibility phenotype.

Chronic obstructive pulmonary disease exacerbations and periodontitis: a possible association

BackgroundThere is an increasing interest concerning the potential link between both chronic obstructive pulmonary disease (COPD) and chronic periodontitis; therefore the association became the research focus.ObjectiveThis study intended to evaluate the potential association between the frequency of COPD exacerbations and chronic periodontitis.Patients and methodsA total of 250 male patients with COPD were included in the study and were categorized into two groups according to the frequency of exacerbations per year: group 1 had patients with frequent exacerbations (having ≥2 exacerbations in last year) and group 2 had patients with infrequent exacerbations (having <2 exacerbations in last year). They were compared regarding age, smoking history, education background, information of their oral hygiene behaviors, calculated modified Medical Research Council dyspnea scale, calculated COPD assessment test, the number of exacerbations and hospitalizations in the past year, prebronchodilator and postbronchodilator spirometry, calculated plaque index, bleeding index, probing pocket depth, clinical attachment level, and measured high-sensitivity C-reactive protein. Correlations between variables were examined. Logistic regression test was performed to explore the concurrent influences of periodontal health variables on the frequency of exacerbations.ResultsThis study evidenced that all periodontal health variables were significantly correlated with smoking status, modified Medical Research Council dyspnea scale, COPD assessment test, number of exacerbations and hospitalizations per year, and C-reactive protein level. Simplified oral hygiene index, plaque index, bleeding index, gingival index, probing pocket depth, and clinical attachment level were significantly correlated with most of the spirometry data.ConclusionPeriodontal health variables were considerably associated with the frequency of COPD exacerbations.

COPD affects worker productivity and health care costs.

PurposeThis study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs. Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated.Patients and methodsThis was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007–2010). Working-age (18–65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits. Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period. Outcomes were evaluated in the first full calendar year after the year of identification (index).ResultsOf the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0). When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001). Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001). Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001).ConclusionWorking-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.

Differential anti-inflammatory effects of budesonide and a p38 MAPK inhibitor AZD7624 on COPD pulmonary cells

BackgroundThe effects of anti-inflammatory drugs in COPD patients may vary between different cell types. The aim of the current study was to assess the anti-inflammatory effects of the corticosteroid budesonide and a p38 MAPK inhibitor (AZD7624) on different cell types obtained from COPD patients and healthy controls.MethodsEight healthy smokers, 16 COPD infrequent exacerbators, and 16 frequent COPD exacerbators (≥2 exacerbations in the last year) were recruited for bronchoscopy and blood sampling. The anti-inflammatory effects of budesonide and AZD7624 were assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages and peripheral blood mononuclear cells and polyinosinic:polycytidylic acid-stimulated bronchial epithelial cells.ResultsThe anti-inflammatory effects of budesonide varied greatly within a patient according to the cell type studied. Bronchial epithelial cells showed the lowest sensitivity to budesonide, while peripheral blood mononuclear cells showed the greatest sensitivity. AZD7624 had a greater effect than budesonide on cytokine production from bronchial epithelial cells. Exacerbation frequency did not influence corticosteroid sensitivity.ConclusionWe observed variable corticosteroid and p38 MAPK inhibitor anti-inflammatory responses within the same individual depending on the cell type studied. These findings support the use of multiple anti-inflammatory strategies in COPD patients due to differences between cell types.

Home Non-Invasive Ventilation for COPD: How, Who and When?

Patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure have high levels of morbidity and mortality. The clinical efficacy of long term home oxygen therapy has been well documented in this patient group but despite the efficacy of non-invasive ventilation (NIV) during acute decompensated respiratory failure the addition of home NIV has been associated with equivocal results. The physiological efficacy of home NIV to improve gas exchange in chronic stable hypercapnic respiratory failure has been proven in small studies but larger clinical trials failed to translate this into clinical efficacy. Criticisms of early clinical trials include the use of marginally hypercapnic patients and failure to demonstrate effective delivery of home NIV. When considering recent trial data it is important to clearly evaluate the patient phenotype and timing and delivery of NIV. Recent data supports the delivery of home NIV in patients with chronic hypercapnia (PaCO2>7kPa or 50mmHg) and the frequent or infrequent exacerbator phenotype. Importantly in the frequent exacerbator the timing of the assessment needs to be in the recovery phase, 2-4 weeks after resolution of acute acidosis, to delineate transient from persistent hypercapnia. In patient with persistent hypercapnia NIV must be titrated to achieve control of sleep disordered breathing with the aim of improving daytime respiratory failure. Furthermore there are observational data to support the use of home positive airway pressure therapy (NIV or continuous positive airway pressure; CPAP) in patients with COPD and obstructive sleep apnoea (OSA) both with and without hypercapnia.

Influecence of cardiovascular risk factors on health related quality of life in patients with chronic obstructive pulmonary disease. Differences between frequent and infrequent exacerbator phenotype

Influecence of cardiovascular risk factors on health related quality of life in patients with chronic obstructive pulmonary disease. Differences between frequent and infrequent exacerbator phenotype

Home Non-Invasive Ventilation for COPD: How, Who and When?

Patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure have high levels of morbidity and mortality. The clinical efficacy of long term home oxygen therapy has been well documented in this patient group but despite the efficacy of non-invasive ventilation (NIV) during acute decompensated respiratory failure the addition of home NIV has been associated with equivocal results. The physiological efficacy of home NIV to improve gas exchange in chronic stable hypercapnic respiratory failure has been proven in small studies but larger clinical trials failed to translate this into clinical efficacy. Criticisms of early clinical trials include the use of marginally hypercapnic patients and failure to demonstrate effective delivery of home NIV. When considering recent trial data it is important to clearly evaluate the patient phenotype and timing and delivery of NIV. Recent data supports the delivery of home NIV in patients with chronic hypercapnia (PaCO2>7kPa or 50mmHg) and the frequent or infrequent exacerbator phenotype. Importantly in the frequent exacerbator the timing of the assessment needs to be in the recovery phase, 2-4 weeks after resolution of acute acidosis, to delineate transient from persistent hypercapnia. In patient with persistent hypercapnia NIV must be titrated to achieve control of sleep disordered breathing with the aim of improving daytime respiratory failure. Furthermore there are observational data to support the use of home positive airway pressure therapy (NIV or continuous positive airway pressure; CPAP) in patients with COPD and obstructive sleep apnoea (OSA) both with and without hypercapnia.

A study of clinical/biological markers of exacerbation/progression in a cohort of patients admitted with acute excerbation of COPD

Background:Exacerbations of chronic obstructive pulmonary disease increases the morbidity, hospital admissions, mortality, and strongly influence health-related quality of life. The aims of this study to know the Clinical profile of COPD and acute exacerbation, Role of clinical markers in diagnosis and follow up of exacerbation.Methods: A prospective study of a cohort of 60 patients hospitalized for AECOPD was undertaken to identify markers for frequent exacerbation and progression of disease. Advised to fill the SGRQ questionnaire, At the time of discharge 6MWT done and analyzed. C Reactive protein levels at the time of admission done and analyzed. Sputum grams stain culture, total counts and differential counts done and analyzed. At the time of discharge spirometry done both pre and post bronchodilators by using asthalin inhaler with or without spacer, results were analyzed.Results:There was statistically significant drop in the SPO2 levels in frequent exacerbators over 6 months follow up time. There was statistically significant elevation of sputum Neutrophil counts in frequent exacerbators and Eosinophil counts in infrequent exacerbators, there was a drop in the CRP levels of from the time of initial exacerbation to 6 months follow up time. There was statistically significant drop in FEV1 in frequent exacerbators over 6 months follow up study. The drop of 6MWT was more in patients, who had frequent exacerbations.Conclusions:Patients with more frequent exacerbation have more symptoms, drop in the saturation level and have more sputum neutrophil counts. Patients with more frequent exacerbations will have more deterioration of lung functions (FEV1.6MWT).