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1.  Effects of telephone health mentoring in community-recruited chronic obstructive pulmonary disease on self-management capacity, quality of life and psychological morbidity: a randomised controlled trial 
BMJ Open  2013;3(9):e003097.
Objectives
To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease (COPD).
Design
Cluster randomised controlled trial.
Setting
Tasmanian general practices: capital city (11), large rural (3), medium rural (1) and small rural (16).
Participants
Patients were invited (1207) from general practitioner (GP) databases with COPD diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176) and excluded (criteria: smoking history or previous study, 68). Spirometry testing (342) confirmed moderate or severe COPD in 182 (53%) patients.
Randomisation
By random numbers code, block stratified on location, allocation by sequentially numbered, opaque and sealed envelopes.
Intervention
Health mentor (HM) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting: problem solving, decision-making and action planning. Control: usual care (UC) group received GP care plus non-interventional brief phone calls.
Outcomes
Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George’s Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress Disorder Checklist, Satisfaction with life and hospital admissions (secondary).
Results
182 participants with COPD (age 68±8 years, 62% moderate COPD and 53% men) were randomised (HM=90 and UC=92). Mixed model regression analysis accounting for clustering, adjusting for age, gender, smoking status and airflow limitation assessed efficacy (regression coefficient, β, reported per 6-month visit). There was no difference in quality of life between groups, but self-management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to 0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both groups (HADS A 0.35; 95% CI −0.65 to −0.04) and coping capacity improved (PIH coping 0.15; 95% CI 0.04 to 0.26).
Conclusions
Health mentoring improved self-management capacity but not quality of life compared to regular phone contact, which itself had positive effects where decline is generally expected.
doi:10.1136/bmjopen-2013-003097
PMCID: PMC3773640  PMID: 24014482
Preventive Medicine; Primary Care
2.  Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010–11 Seasons: A Test-negative Observational Study 
PLoS ONE  2013;8(7):e68760.
Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.
doi:10.1371/journal.pone.0068760
PMCID: PMC3712933  PMID: 23874754
3.  Changes in Airway Histone Deacetylase2 in Smokers and COPD with Inhaled Corticosteroids: A Randomized Controlled Trial 
PLoS ONE  2013;8(5):e64833.
The expression of HDAC2 is reported as reduced in chronic obstructive pulmonary disease (COPD). We assessed HDAC2 expression within the airways of smokers and subjects with COPD and effects of inhaled corticosteroids (ICS), using immuno-histology to contrast with previous molecular methodology.
Endobronchial biopsies (ebb) from current smokers with COPD (COPD-CS; n = 15), ex-smokers with COPD (COPD-ES; n = 17), smokers with normal lung function (NS; n = 16) and normal controls (NC; n = 9) were immunostained for HDAC2. A double-blinded, randomized, placebo-controlled 6 months intervention study assessed effects of ICS on HDAC2 in 34 COPD subjects.
There was no difference in epithelial HDAC2 staining in all groups. There was a significant reduction in total cell numbers in the lamina propria (LP) in COPD-CS and NS (p<0.05). LP cellularity correlated inversely with smoking history in COPD-CS (R = −0.8, p<0.003). HDAC2 expression increased markedly in NS (p<0.001); in contrast COPD-CS was associated with suppressed signal (p<0.03), while normal in COPD-ES. ICS did not affect HDAC2 cell staining.
Our findings suggest that airway HDAC2 expression is increased in the LP by smoking itself, but is reduced in COPD. Ex-smokers have normalised HDAC2 cell expression, but ICS had no effect. The paper emphasise the pit-falls of relying on molecular data alone to define airway changes.
Clinical Trial Registration Information:
Name of registry
The Australian New Zealand Clinical Trials Registry (ANZCTR)
Registry number
ACTRN12612001111864
doi:10.1371/journal.pone.0064833
PMCID: PMC3661479  PMID: 23717666
4.  Clinical diaries in COPD: compliance and utility in predicting acute exacerbations 
Background
Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor. Their use in chronic obstructive pulmonary disease (COPD) and impact on the prevention and treatment of exacerbations is poorly researched.
Methods
We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations. Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication.
Results
Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%. Participants educated to primary school level only had lower compliance (P = 0.05). Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days. Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use.
Conclusion
Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level. Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency.
doi:10.2147/COPD.S32222
PMCID: PMC3402058  PMID: 22848156
chronic obstructive pulmonary disease; daily diary; secondary prevention
5.  Clinical trial of community nurse mentoring to improve self-management in patients with chronic obstructive pulmonary disease 
Background
Chronic obstructive pulmonary disease (COPD) impacts on quality of life and is characterized by exacerbations, which increase health care utilization. Developing self-management behaviors of people with COPD is an attractive strategy to reduce exacerbations.
Methods
We investigated the effect of a program to increase self-management behaviors delivered by community health nurses, compared with usual care, on health-related quality of life and health care utilization in people with COPD following hospitalization. Participants were recruited during an admission to hospital and allocated according to domicile. The mentor role was to develop self-management strategies collaboratively over the 12-month study duration. Outcomes included quality of life and health care utilization.
Results
Linear mixed models analyses found a significant benefit in the physical functioning and general health components of the short-form SF-36 questionnaire for the mentored arm, with the average difference between interventions being 5.60 and 4.14, respectively, over 12 months. Survival analysis using a combined endpoint of time to next acute exacerbation requiring rehospitalization or death found a significant benefit favoring the mentored group (P = 0.037).
Conclusion
A mentoring program designed to improve self-management behaviors in people with COPD following hospitalization increased some quality of life domains and improved important clinical outcomes.
doi:10.2147/COPD.S32220
PMCID: PMC3402057  PMID: 22848153
pulmonary disease; chronic obstructive; secondary prevention; quality of life; hospitalization
6.  Vessel-Associated Transforming Growth Factor-Beta1 (TGF-β1) Is Increased in the Bronchial Reticular Basement Membrane in COPD and Normal Smokers 
PLoS ONE  2012;7(6):e39736.
Background
Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity. There are only limited data about its role in airway remodeling in COPD. We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD). This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.
Methodology/Principal Findings
Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls. The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups. Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3. Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls. TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0–12.7), 3.4 (0.0–8.1) and 1.0 (0.0–6.3) vs. 0.0 (0.0–7.0), p<0.05]. Percentage of vessels stained was also increased in these clinical groups. Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.
Conclusions/Significance
Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD.
doi:10.1371/journal.pone.0039736
PMCID: PMC3387255  PMID: 22768115
7.  Supporting health behaviour change in chronic obstructive pulmonary disease with telephone health-mentoring: insights from a qualitative study 
BMC Family Practice  2012;13:55.
Background
Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring.
Methods
Community nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change, using a framework of health behaviours; ‘SNAPPS’ Smoking, Nutrition, Alcohol, Physical activity, Psychosocial well-being, and Symptom management, through regular phone calls over 12 months. Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted. Interviews were analysed using iterative thematic and interpretative content approaches by two investigators.
Results
Of 90 participants allocated to health-mentoring, 65 (72%) were invited for interview at 12-month follow up. The 44 interviewees, 75% with moderate COPD, had a median of 13 mentor contacts over 12 months, range 5–20. Interviewed participants (n = 44, 55% male, 43% current smokers, 75% moderate COPD) were representative of the total group with a mean age 65 years while 82% had at least one additional co-morbid chronic condition. Telephone delivery was highly acceptable and enabled good rapport. Participants rated ‘being listened to by a caring health professional’ as very valuable. Three participant groups were identified by attitude to health behaviour change: 14 (32%) actively making changes; 18 (41%) open to and making some changes and 12 (27%) more resistant to change. COPD severity or current smoking status was not related to group category. Mentoring increased awareness of COPD effects, helping develop and personalise behaviour change strategies, even by those not actively making changes. Physical activity was targeted by 43 (98%) participants and smoking by 14 (74%) current smokers with 21% reporting quitting. Motivation to maintain changes was increased by mentor support.
Conclusions
Telephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care. Health behaviours targeted by this population, mostly with moderate disease, were mainly physical activity and smoking reduction or cessation. Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change.
Trial registration
ACTR12608000112368
doi:10.1186/1471-2296-13-55
PMCID: PMC3411441  PMID: 22694996
Health-mentoring; Behaviour change; Primary care; Chronic obstructive pulmonary disease; Physical activity; Smoking
8.  Reticular Basement Membrane Vessels Are Increased in COPD Bronchial Mucosa by Both Factor VIII and Collagen IV Immunostaining and Are Hyperpermeable 
Journal of Allergy  2012;2012:958383.
Background and Objective. Using Collagen IV staining, we have previously reported that the reticular basement membrane (Rbm) is hypervascular and the lamina propria (LP) is hypovascular in COPD airways. This study compared Collagen IV staining with vessels marked with anti-Factor VIII and examined vessel permeability in bronchial biopsies from COPD and normal subjects using albumin staining. Results. Anti-Collagen IV antibody detected more vessels in the Rbm (P = 0.002) and larger vessels in both Rbm (P < 0.001) and LP (P = 0.003) compared to Factor VIII. COPD airways had more vessels (with greater permeability) in the Rbm (P = 0.01) and fewer vessels (with normal permeability) in the LP compared to controls with both Collagen IV and Factor VIII antibodies (P = 0.04 and P = 0.01). Conclusion. Rbm vessels were increased in number and were hyperpermeable in COPD airways. Anti-Collagen IV and anti-Factor VIII antibodies did not uniformly detect the same vessel populations; the first is likely to reflect larger and older vessels with the latter reflecting smaller, younger vessels.
doi:10.1155/2012/958383
PMCID: PMC3303780  PMID: 22500190
9.  Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease 
Respiratory Research  2011;12(1):130.
Background
The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also present in the basal epithelium. Such changes are likely hallmarks of epithelial mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.
Methods
Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells). The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope". Slides were double stained for S100A4 and cytokeratin(s).
Results
In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003. Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003. Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.
Conclusions
These data provide additional support for active EMT in COPD airways.
doi:10.1186/1465-9921-12-130
PMCID: PMC3198934  PMID: 21970519
cytokeratin; clefts; epithelial mesenchymal transition (EMT); inflammatory cells and S100A4
10.  Clinical and epidemiological profile of patients with severe H1N1/09 pandemic influenza in Australia and New Zealand: an observational cohort study 
BMJ Open  2011;1(1):e000100.
Background
Pandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity.
Methods
The authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand.
Results
During the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza.
Conclusions
The clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.
Article summary
Article focus
We performed an observational study of patients with H1N1/09 and seasonal strains of influenza in 2009, based on active surveillance at nine sentinel hospitals.
We explored differences between patients with H1N1/09 influenza infection and those with seasonal influenza infections.
Key messages
This study found that the clinical features of H1N1/09 influenza were similar in hospitalised patients, similar to previous community-based studies.
The finding that H1N1/09 influenza was associated with more severe disease reconciles apparently contradictory data suggesting no differences in community studies, but unprecedented use of critical care services.
Strengths and limitations of this study
This surveillance system was rapidly established, and initial data collection was retrospective from the medical record where symptoms were not always well documented. Despite high levels of awareness in medical staff, clinical testing criteria were operating during the period of the study and were likely to bias the proportion of patients reporting fever and respiratory symptoms. Nucleic-acid detection using PCR is regarded as the gold standard for diagnosis, but our experience with discordant results on repeated testing suggested that it may not be completely sensitive. This study does not encompass the full duration of the epidemic which was waning in several states (notably Victoria and New South Wales) at the commencement of the study period. Although several hospitals provided maternity and paediatric services, these patient groups are likely to be under-represented in this series. The population served by the sentinel hospitals is not known, and thus we were not able to establish a disease incidence rate.
This large study captured all admissions with influenza at multiple hospitals across Australia and New Zealand. All cases were confirmed by nucleic acid detection with clinical details collected by research staff.
doi:10.1136/bmjopen-2011-000100
PMCID: PMC3191436  PMID: 22021761
Infectious diseases; epidemiology; infection control; emergency medicine; toxinology; prehospital; evenoming; anaphylaxis; asthma; television; respiratory; patient reported outcomes airways disease; COPD
11.  Albuterol enantiomer levels, lung function and QTc interval in patients with acute severe asthma and COPD in the emergency department 
Background
This observational study was designed to investigate plasma levels of albuterol enantiomers among patients with acute severe asthma or COPD presenting to the emergency department, and the relationship with extra-pulmonary cardiac effects (QTc interval) and lung function. Recent reviews have raised concerns about the safety of using large doses of β2-agonists, especially in patients with underlying cardiovascular comorbidity. It has been demonstrated that significant extrapulmonary effects can be observed in subjects given nebulised (R/S)-albuterol at a dose of as little as 6.5 mg.
Methods
Blood samples were collected and plasma/serum levels of (R)- and (S)-albuterol enantiomers were determined by LC-MS and LC-MS/MS assay. Extra-pulmonary effects measured at presentation included ECG measurements, serum potassium level and blood sugar level, which were collected from the hospital medical records.
Results
High plasma levels of both enantiomers were observed in some individuals, with median (range) concentrations of 8.2 (0.6-24.8) and 20.6 (0.5-57.3) ng/mL for (R)- and (S)- albuterol respectively among acute asthma subjects, and 2.1 (0.0-16.7) to 4.1 (0.0-36.1) ng/mL for (R)- and (S)- albuterol respectively among COPD subjects. Levels were not associated with an improvement in lung function or adverse cardiac effects (prolonged QTc interval).
Conclusions
High plasma concentrations of albuterol were observed in both asthma and COPD patients presenting to the emergency department. Extra-pulmonary cardiac adverse effects (prolonged QTC interval) were not associated with the plasma level of (R)- or (S)-albuterol when administered by inhaler in the emergency department setting. Long-term effect(s) of continuous high circulating albuterol enantiomer concentrations remain unknown, and further investigations are required.
doi:10.1186/1865-1380-4-30
PMCID: PMC3135507  PMID: 21676212
12.  "Bong lung" in cystic fibrosis: a case report 
Introduction
Marijuana or "bong" lung has been recently described. Subjects typically develop large peripheral paraseptal lung bullae and are predisposed to spontaneous pneumothoraces. The underlying mechanism for bullae formation is uncertain, but probably relates to direct lung toxicity and repeated barotrauma as the smoker performs frequent valsalva manoeuvres in an attempt to derive a greater drug effect.
Case presentation
We describe a case of probable "bong lung" occurring in a 23-year-old Caucasian man with cystic fibrosis who had a history of recurrent pneumothoraces and unusual findings on sputum cytology.
Conclusion
Our case highlights the importance of questioning young adult cystic fibrosis patients about illicit drug use and the utility of sputum cytology and computed tomography scanning when patients present with pneumothoraces and deteriorations in clinical status.
doi:10.1186/1752-1947-4-371
PMCID: PMC2998526  PMID: 21092085
13.  Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial 
Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.
Design Cluster randomised controlled parallel group trial.
Setting Ambulance service in Hobart, Tasmania, Australia.
Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.
Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.
Main outcome measure Prehospital or in-hospital mortality.
Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.
Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.
Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291.
doi:10.1136/bmj.c5462
PMCID: PMC2957540  PMID: 20959284
14.  Assessment of airway inflammation using sputum, BAL, and endobronchial biopsies in current and ex-smokers with established COPD 
Rationale
Smoking effects on physiological and gross pathology in chronic obstructive pulmonary disease (COPD) are relatively well described. However, there is little known in COPD about the detailed interrelationships between lung function and inflammatory profiles in different airway compartments from the same individual and whether airway inflammation in these different compartments differs in ex- and current smokers with established COPD.
Objectives
We compared sputum, bronchoalveolar (BAL), and airway wall inflammatory profiles in current versus ex-smokers and related this to smoking intensity and lung function in 17 current and 17 ex-smokers with mild to moderate COPD.
Results
Current smokers had more sputum mast cells (% differential and absolute numbers), whereas ex-smokers had increased sputum neutrophils. In BAL, there was a significant increase in eosinophils in current smokers, but ex-smokers had significantly increased neutrophils, lymphocytes, and epithelial cells. There were no cell profile differences observed in airway biopsies between current and ex-smokers and there were no correlations between the individual inflammatory cell populations in any of the airway compartments. In current smokers only, smoking intensity was negatively correlated with lung function, and associated with a reduction in overall cellularity of both sputum and BAL.
Conclusion
Airway inflammation persists in ex-smokers with COPD, but differs from COPD current smokers. The impact of smoking appears to vary in different airway compartments and any direct relationships between cellularity and lung function tended to be negative, ie, worse lung function indicated the presence of fewer cells.
doi:10.2147/COPD.S11343
PMCID: PMC2962298  PMID: 21037956
current smokers; ex-smokers; airway cellularity; sputum; BAL; endobronchial biopsies
15.  Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study 
Respiratory Research  2010;11(1):105.
Background
Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.
Methods
To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.
Results
Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).
Conclusions
Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.
doi:10.1186/1465-9921-11-105
PMCID: PMC2918561  PMID: 20670454
16.  Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease 
Histopathology  2012;60(6):964-970.
Aims
This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.
Methods and results
Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied. The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls. Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4–68.5) versus 5.3% (0.0–21.7) versus 1.5% (0.0–15.1), P < 0.001]. The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6–23.0) versus 4.5 (0.0–26.4) versus 4.4 (0.4–8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115–2456) versus 462 (0–3263) versus 426 (32–2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.
Conclusions
The characteristics of Rbm remodelling are quite different in asthma and COPD.
doi:10.1111/j.1365-2559.2011.04147.x
PMCID: PMC3465784  PMID: 22320998
airway remodelling; asthma; bronchial biopsies; chronic obstructive pulmonary disease; reticular basement membrane

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