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Background: Falls are frequent in people with chronic obstructive pulmonary disease (COPD) and related to increased morbidity, mortality, and health care costs in older adults. This systematic review aims to synthesise the falls outcomes and to examine risk factors for falls in the COPD literature., Methods: The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42015017257). Searches were updated and operated in five electronic databases in December 2019 for studies reporting falls outcomes and risk factors in people with COPD. Meta-analyses were conducted on the prevalence of fallers and frequent fallers. Quality assessment appraised the risk of bias of included articles., Results: Twenty-three studies met the eligibility criteria and were retained after the full-text review. In the meta-analyses, the pooled prevalence of COPD fallers was 30% (95%CI 19%-42%), and the pooled prevalence of frequent fallers (≥2 falls in the analysed period of occurrence) was 24% (95%CI 2%-56%). The falls incidence rate in stable COPD varied from 1.17 to 1.49 falls/person-year. Different study methodologies were identified. Age, female gender, falls history, the number of medications, comorbidities, coronary heart disease, use of supplemental oxygen, impaired balance performance and smoking history were risk factors for falls identified in stable COPD., Conclusion: Prevalence of fallers, frequent fallers, and falls incidence rate have been reported in the COPD literature using a varying methodology. People with stable COPD present with ageing and disease-related risk factors for falls. Further research using the recommended prospective recording is needed in COPD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is an incurable inflammatory lung disease that afflicts millions of people worldwide, and it is the fourth leading cause of death. Systemic comorbidities affecting the heart, skeletal muscle, bone, and metabolism are major contributors to morbidity and mortality. Given the surprising finding in large prospective clinical biomarker studies that peripheral white blood cell count is more closely associated with disease than inflammatory biomarkers, we probed the role of blood growth factors. Using the SHIP-1-deficient COPD mouse model, which manifests a syndrome of destructive lung disease and a complex of comorbid pathologies, we have identified a critical and unexpected role for granulocyte-CSF (G-CSF) in linking these conditions. Deletion of G-CSF greatly reduced airway inflammation and lung tissue destruction, and attenuated systemic inflammation, right heart hypertrophy, loss of fat reserves, and bone osteoporosis. In human clinical translational studies, bronchoalveolar lavage fluid of patients with COPD demonstrated elevated G-CSF levels. These studies suggest that G-CSF may play a central and unforeseen pathogenic role in COPD and its complex comorbidities, and identify G-CSF and its regulators as potential therapeutic targets.

Background and Objective: Non-invasive ventilation (NIV) improves clinical outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal model of care remains unknown., Methods: We conducted a prospective observational non-inferiority study comparing three models of NIV care: general ward (Ward) (1:4 nurse to patient ratio, thrice weekly consultant ward round), a high dependency unit (HDU) (1:2 ratio, twice daily ward round) and an intensive care unit (ICU) (1:1 ratio, twice daily ward round) model in three similar teaching tertiary hospitals. Changes in arterial blood gases (ABG) and clinical outcomes were compared and corrected for differences in AECOPD severity (Blood urea > 9 mmol/L, Altered mental status (Glasgow coma scale (GCS) < 14), Pulse > 109 bpm, age > 65 (BAP-65)) and co-morbidities. An economic analysis was also undertaken., Results: There was no significant difference in age (70 ± 10 years), forced expiratory volume in 1 s (FEV 1 ) (0.84 ± 0.35 L), initial pH (7.29 ± 0.08), partial pressure of CO 2 in arterial blood (PaCO 2 ) (72 ± 22 mm Hg) or BAP-65 scores (2.9 ± 1.01) across the three models. The Ward achieved an increase in pH (0.12 ± 0.07) and a decrease in PaCO 2 (12 ± 18 mm Hg) that was equivalent to HDU and ICU. However, the Ward treated more patients (38 vs 28 vs 15, P < 0.001), for a longer duration in the first 24 h (12.3 ± 4.8 vs 7.9 ± 4.1 vs 8.4 ± 5.3 h, P < 0.05) and was more cost-effective per treatment day ($AUD 1231 ± 382 vs 1745 ± 2673 vs 2386 ± 1120, P < 0.05) than HDU and ICU. ICU had a longer hospital stay (9 ± 11 vs 7 ± 7 vs 13 ± 28 days, P < 0.002) compared with the Ward and HDU. There was no significant difference in intubation rate or survival., Conclusion: In acute hypercapnic Chronic obstructive pulmonary disease (COPD) patients, the Ward model of NIV care achieved equivalent clinical outcomes, whilst being more cost-effective than HDU or ICU models., (© 2017 Asian Pacific Society of Respirology.)

Individuals with chronic obstructive pulmonary disease (COPD) have demonstrated balance impairment and a higher fall incidence. However, these have not been investigated in acute exacerbations of the disease (ECOPD). This study evaluates balance in patients during an ECOPD compared to stable COPD and healthy controls, and examines the fall incidence rate after hospitalisation due to ECOPD compared to individuals with stable COPD. Balance performance of 26 hospitalised patients with ECOPD was compared to 26 community-dwelling participants with stable COPD and 25 matched healthy controls. Balance was evaluated using computerised posturography and the Berg Balance Scale (BBS). Prospective falls were monitored by monthly calendars for 12 months in both COPD groups. Compared to controls, greater balance impairment was observed during ECOPD for most posturography variables across standing conditions (p ≤ 0.05). Both COPD groups had worse BBS scores (p ≤ 0.05) compared to controls. Increased dyspnoea and reduced quadriceps' strength were associated with impaired balance performance. A higher fall incidence (1.76 falls/person/year) was observed following hospitalisation in patients with ECOPD compared to stable COPD (0.53 falls/person/year) at 12 months. Patients with ECOPD demonstrate balance impairments which are associated with increased dyspnoea and reduced muscle strength. Balance impairment during ECOPD may contribute to a high incidence of falls following hospitalisation.

Background: In patients with chronic obstructive pulmonary disease (COPD) and co-morbid cardiovascular disease, emerging evidence suggests a benefit in commencing cardioselective beta-blockers., Aim: Our objective was to determine the safety of beta-blocker commencement during hospitalisation for acute exacerbation of COPD., Methods: A retrospective cohort study of 1071 patients hospitalised for acute exacerbation of COPD was conducted across two tertiary hospitals over a 12-month period. We identified 36 patients in whom beta-blocker therapy was commenced during admission. The primary outcome of the study was to assess cardiovascular and respiratory adverse events related to the commencement of beta-blocker therapy., Results: The most common indications for beta-blockers were atrial fibrillation (53%) and acute coronary syndrome (36%). Metoprolol was the most commonly prescribed beta-blocker (75%). No patients suffered clinically significant declines of respiratory function following the commencement of a beta-blocker, including worsening respiratory symptoms, oxygen, bronchodilator or ventilation requirements. These results were demonstrable in patients with reversible airways disease and advanced COPD. Only one patient (2.8%) experienced symptomatic hypotension after 48 h of therapy., Conclusion: The commencement of cardioselective beta-blockers during acute exacerbations of COPD appears to be well-tolerated., (© 2017 Royal Australasian College of Physicians.)

The use of beta-blockers in patients with chronic obstructive pulmonary disease and co-morbid cardiovascular disease is controversial, despite increasing evidence to support their use as safe and efficacious. This study retrospectively assessed the rates of beta-blocker prescription in patients admitted to two Australian tertiary hospitals for acute exacerbation of chronic obstructive pulmonary disease. This revealed that less than half of patients (45%) with known cardiac indications were receiving beta-blocker therapy, evident across all degrees of airways disease severity. Further work is needed to ensure that medical management of this patient group is optimised., (© 2016 Royal Australasian College of Physicians.)

Background: Peripheral pulmonary lesion (PPL) is a common scenario in patients with chronic obstructive pulmonary disease (COPD) and represents a high risk of malignancy. Severe COPD is associated with higher complication rates following percutaneous biopsy, and routine bronchoscopy. Safety and diagnostic performance of radial endobronchial ultrasound bronchoscopy (R-EBUS) in patients with advanced COPD has not been previously assessed., Methods: We examined a retrospective cohort of patients with advanced COPD undergoing R-EBUS for the evaluation of PPL., Results: During the study period, 92 patients underwent 94 R-EBUS procedures. In 50 cases, patients had severe obstructive deficit with mean forced expiratory volume in 1 second (FEV1) of 1.01±0.28 L, and FEV1% predicted 39.7±8.2. In 44 cases, patients had mild-moderate obstruction with severe diffusion impairment, with mean diffusion capacity for carbon monoxide% predicted of 41.2±7.9. Pneumothorax requiring intercostal catheter insertion occurred in 2 patients (2.1%). In 10 cases (10.6%; 95% confidence interval, 4.4%-16.8%) patients experienced acute respiratory failure. Diagnostic yield was 63% (59/94) and overall sensitivity for primary lung malignancy was 70% (53/76). Nine patients had a diagnosis on R-EBUS obviating lung resection., Conclusion: R-EBUS is safe and accurate for the investigation of PPL in patients with advanced COPD.

The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.

Background and Objective: Despite evidence of an increased fall risk in people with chronic obstructive pulmonary disease (COPD), there is a paucity of prospective fall data in this population. This preliminary study aimed to prospectively examine the prevalence rate, incidence rate and associated risk factors for falls in a sample of community-dwelling people with COPD over 1 year., Methods: Forty-one participants with stable COPD (mean ± SD) aged 71 ± 8 years with a forced expiratory volume in 1 s of 45.1 ± 16.2% predicted were included. At baseline, participants' demographic, physical function and fall-related measures were documented. Falls were monitored for 12 months following initial assessments., Results: The prevalence of people having falls was 40% (95% CI: 24-56%); amongst these, 75% had frequent falls. The overall fall incidence rate was 1.17 falls/person-year. Risk factors associated with a higher fall incidence rate ratio (IRR) in COPD were: number of pack-years (IRR: 1.02; 95%CI: 1.00,1.04), comorbidities (IRR: 2.02; 95%CI: 1.42,3.06), number of medications (IRR: 1.15; 95%CI: 1.00,1.34), history of falls in the previous year (IRR: 1.89; 95%CI: 1.10,3.34), fear of falling (IRR: 1.08; 95% CI: 1.02,1.14) and higher score in a fall risk assessment questionnaire for older adults (IRR: 1.14; 95% CI: 1.05,1.25); P ≤ 0.05. When adjusted for age, only pack-years (P = 0.01), number of comorbidities (P < 0.001) and history of falls (P = 0.03) were related to an increased fall incidence., Conclusions: These preliminary findings demonstrated the fall prevalence and incidence rate in community-dwelling people with stable COPD and identified prospective risk factors for an increased fall incidence, which suggest potential mitigation strategies., (© 2015 Asian Pacific Society of Respirology.)

Background: Increased fear of falling (FOF) has been associated with impaired physical function, reduced physical activity and increased fall risk in older adults. Preliminary evidence suggests that individuals with chronic obstructive pulmonary disease (COPD) may have an increased FOF. This study aims to compare the level of FOF in people with COPD with healthy controls, and to determine the associations between FOF and measures of physical function, physical activity and fall risk in COPD., Methods: FOF was assessed in 40 participants with COPD and 25 age- and gender-matched controls using the Falls Efficacy Scale-International (FES-I). Physical function was evaluated using quadriceps hand-held dynamometry, the Berg Balance Scale and the Six-minute Walk Test. Associations between FOF, physical activity and fall risk were evaluated using the Physical Activity Scale for the Elderly and the Falls Risk in Older People - Community Setting. Pearson's correlation coefficient and stepwise multivariate linear regression were used., Results: Individuals with COPD (mean ± SD; age: 71 ± 8 years, FEV1: 45 ± 16 %pred) had higher FOF compared to controls (FES-I: 25.0 ± 7.9 vs 20.2 ± 5.2, p=0.01). Higher FOF was associated with lower quadriceps strength (p=0.02) and an impaired balance (p < 0.01); these explained 26% of the FOF variance. Reduced levels of physical activity (p=0.01) and a higher fall risk (p < 0.01) were associated with an increased FOF in COPD., Conclusion: People with COPD have a higher FOF compared to the healthy peers, which is related to lower quadriceps muscle strength, impaired balance, lower levels of physical activity and an increased fall risk., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Serum amyloid A (SAA) is expressed locally in chronic inflammatory conditions such as chronic obstructive pulmonary disease (COPD), where macrophages that do not accord with the classic M1/M2 paradigm also accumulate. In this study, the role of SAA in regulating macrophage differentiation was investigated in vitro using human blood monocytes from healthy subjects and patients with COPD and in vivo using an airway SAA challenge model in BALB/c mice. Differentiation of human monocytes with SAA stimulated the proinflammatory monokines IL-6 and IL-1β concurrently with the M2 markers CD163 and IL-10. Furthermore, SAA-differentiated macrophages stimulated with lipopolysaccharide (LPS) expressed markedly higher levels of IL-6 and IL-1β. The ALX/FPR2 antagonist WRW4 reduced IL-6 and IL-1β expression but did not significantly inhibit phagocytic and efferocytic activity. In vivo, SAA administration induced the development of a CD11c(high)CD11b(high) macrophage population that generated higher levels of IL-6, IL-1β, and G-CSF following ex vivo LPS challenge. Blocking CSF-1R signaling effectively reduced the number of CD11c(high)CD11b(high) macrophages by 71% and also markedly inhibited neutrophilic inflammation by 80%. In conclusion, our findings suggest that SAA can promote a distinct CD11c(high)CD11b(high) macrophage phenotype, and targeting this population may provide a novel approach to treating chronic inflammatory conditions associated with persistent SAA expression., (© FASEB.)

Neutrophilic inflammation persists in COPD despite best current therapies and it is particularly resistant to inhaled glucocorticosteroids. Persistent neutrophil activation not only contributes to matrix breakdown, but can maintain inflammation through the release of endogenous damage associated molecule patterns (DAMPs). Inhibiting excessive neutrophilic inflammation is challenging as many pathogen recognition receptors can initiate migration and the targeting of downstream signaling molecules may compromise essential host defense mechanisms. Here, we discuss new strategies to combat this inflammation in COPD by focusing on the anti-inflammatory role of ALX/FPR2 receptors. ALX/FPR2 is a promiscuous G-protein coupled receptor (GPCR) responding to lipid and peptide agonists that can either switch on acute inflammation or promote resolution of inflammation. We highlight this receptor as an emerging target in the pathogenesis of COPD because known ALX/FPR2 endogenous agonists are enriched in COPD. Serum Amyloid A (SAA) has recently been discovered to be abundantly expressed in COPD and is a potent ALX/FPR2 agonist that unlike almost all other inflammatory chemoattractants, is induced by glucocorticosteroids. SAA not only initiates lung inflammation via ALX/FPR2 but can allosterically modify this receptor so that it no longer transduces pro-resolving signals from endogenous lipoxins that would otherwise promote tissue healing. We propose that there is an imbalance in endogenous and microbial ALX/FPR2 receptor agonists in the inflamed COPD lung environment that oppose protective anti-inflammatory and pro-resolution pathways. These insights open the possibility of targeting ALX/FPR2 receptors using synthetic agonists to resolve persistent neutrophilic inflammation without compromising essential host defense mechanisms., (© 2013.)

Objectives: To systematically review the instruments used to assess postural control and fear of falling in people with chronic obstructive pulmonary disease (COPD), and to synthesize and evaluate their breadth of content and measurement properties., Data Sources: MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL, PsycINFO, PEDro, and OTSeeker databases searched in September 2012., Study Selection: Two independent reviewers performed the selection of articles, the ICF linking process and quality assessment. Only quantitative studies were included, irrespective of language or publication date., Data Extraction: This systematic review comprised two phases. Phase 1 aimed to identify the commonly used instruments to assess postural control and fear of falling in the COPD literature. The breadth of content of each instrument was examined based on the International Classification of Functioning, Disability and Health (ICF). In phase 2, a measurement property search filter was adopted and used in four electronic databases to retrieve properties reported in the COPD population. The COSMIN checklist was used to assess the methodological quality of each measurement property reported., Data Synthesis: Seventeen out of 401 publications were eligible in phase 1. Seventeen instruments were identified including 15 for postural control and 2 for fear of falling assessment. The Berg Balance Scale, the Short Physical Performance Battery, and the Activities-specific Balance Confidence (ABC) scale were the most frequently used instruments to assess postural control and fear of falling respectively. The ICF categories covered varied considerably among instruments. The Balance Evaluation Systems test and ABC presented the greatest breadth of content. Measurement properties reported included criterion predictive validity (4 instruments), construct validity (11 instruments) and responsiveness (1 instrument), with inconsistent findings based on 'fair' and 'poor' quality studies., Conclusions: Different instruments with heterogeneous content have been used to assess postural control and fear of falling outcomes. Standardized assessment methods and best evidence on measurement properties is required in the COPD literature., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale: Neutrophilic inflammation is an important pathologic feature of chronic obstructive pulmonary disease (COPD) and infectious exacerbations of COPD. Serum amyloid A (SAA) promotes neutrophilic inflammation by its interaction with lung mucosal ALX/FPR2 receptors. However, little is known about how this endogenous mediator regulates IL-17A immunity., Objectives: To determine whether SAA causes neutrophilic inflammation by IL-17A-dependent mechanisms., Methods: The relationship between SAA and neutrophils was investigated in lung sections from patients with COPD and a chronic mouse model of SAA exposure. A neutralizing antibody to IL-17A was used to block SAA responses in vivo, and a cell-sorting strategy was used to identify cellular sources., Measurements and Main Results: SAA mRNA expression was positively associated with tissue neutrophils in COPD (P < 0.05). SAA predominately promoted expression of the TH17 polarizing cytokine IL-6, which was opposed by 15-epi-lipoxin A4, a counter-regulatory mediator, and ALX/FPR2 ligand. SAA-induced inflammation was markedly reduced by a neutralizing antibody to IL-17A in vivo. Cellular sources of IL-17A induced by SAA include CD4(+) T cells, γδ T cells, and an Epcam(+)CD45(-) population enriched for epithelial cells. SAA promotes expression of IL-17A in γδ T cells and this innate cell proportionally expressed higher levels of IL-17A transcript than CD4(+) T cells or epithelial cells., Conclusions: The SAA-IL-17A axis represents an important innate defense network that may underlie persistent neutrophilic airway inflammation in COPD and modulating the ALX/FPR2 receptor represents a novel approach to targeting aberrant IL-17A-mediated lung immunity.

Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A(4) (LXA(4)) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA(2) 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA(4). Human lung macrophages (CD68(+)) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC(50) 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA(4) but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

Introduction: We investigated the relationship between frequency of exacerbation and duration and change in functional status, as measured by the BODE index in chronic obstructive pulmonary disease (COPD) patients., Methods: This was a longitudinal cohort study of 56 patients with moderate to severe COPD. Body mass index, spirometry, Modified Medical Research Council (MMRC) dyspnoea score and six-minute walk distance (6MWD) were measured annually when the patients were clinically stable. Data on frequency and duration of COPD exacerbations occurring in the community and requiring hospitalisation were collected prospectively. Early stage exacerbations were identified through the use of individualised patient action plans and further reinforced by fortnightly phone contact., Results: At the two-year follow-up, the BODE index increased in 33 patients, remained stable in 18 and decreased in five patients. Patients with increased BODE index had significantly higher hospital presentation rates and longer total bed-days compared to those with stable BODE index. Among the 33 patients with increased BODE index, 20 had lower 6MWD and higher MMRC scores, indicating deteriorating functional status, and 13 had higher levels of airway obstruction. Between these two subgroups, patients with deteriorating functional status had higher exacerbation frequency, longer exacerbation duration and higher inpatient bed-days. Linear regression showed that total annual duration of exacerbation was predictive of change in 6MWD., Conclusion: Change in the BODE index is a sensitive measure of deteriorating functional status in COPD patients. Duration of exacerbation has greater impact on functional status than frequency of exacerbation episodes.

Aim: The aim of this study was to develop a clinical algorithm to assess chronic obstructive pulmonary disease exacerbation severity in a community setting., Background: An important aspect of community management of exacerbations is assessing patient safety. Although researchers have investigated risk factors for rapid deterioration, there is a lack of evidence validating clinical measures of exacerbation severity., Methods: This was a prospective, community-based cohort study of patients enrolled in the Melbourne Longitudinal Chronic Obstructive Pulmonary Disease Cohort. The outreach team collected data on symptom severity at baseline and exacerbation onset using the Medical Research Council Dyspnoea Scale, St George Quality-of-Life Questionnaire and Symptom Severity Index., Results: Ninety-two patients were monitored from 2003 to 2005. There were 148 exacerbations: 121 (82%) were treated at home and 27 (17·5%) required hospitalization. An ordinal logistic regression model demonstrated that a combination of chronic obstructive pulmonary disease severity with dyspnoea and wheeze severity at exacerbation onset could differentiate severe from milder episodes [(OR 7·69, 95%CI: 3·9-11·5, P < 0·01), area under the receiver operating characteristics curve 0·75 (95%CI: 0·65-0·86)]., Conclusion: The majority of chronic obstructive pulmonary disease exacerbations can be safely managed in a community setting, but clinical assessment alone may not be sufficient to identify all patients who will develop complications such as respiratory failure. Further research is needed to validate clinical assessment and decision-making algorithms for community-management of chronic obstructive pulmonary disease exacerbations., (© 2010 Blackwell Publishing Ltd.)

Background: Known inflammatory markers have limited sensitivity and specificity to differentiate viral respiratory tract infections from other causes of acute exacerbation of COPD (AECOPD). To overcome this, we developed a multi-factorial prediction model combining viral symptoms with inflammatory markers., Methods: Interleukin-6 (IL-6), serum amyloid A (SAA) and viral symptoms were measured in stable COPD and at AECOPD onset and compared with the viral detection rates on multiplex PCR. The predictive accuracy of each measure was assessed using logistic regression and receiver operating characteristics curve (ROC) analysis., Results: There was a total of 33 viruses detected at the onset of 148 AECOPD, the majority 26 (79%) were picornavirus. Viral symptoms with the highest predictive values were rhinorrhoea [Odds ratio (OR) 4.52; 95% CI 1.99-10.29; P < 0.001] and sore throat (OR 2.64; 95% CI 1.14-6.08; P = 0.022), combined the AUC ROC curve was 0.67. At AECOPD onset patients experienced a 1.6-fold increase in IL-6 (P = 0.008) and 4.5-fold increase in SAA (P < 0.001). The addition of IL-6 to the above model significantly improved diagnostic accuracy compared with symptoms alone (AUC ROC 0.80 (P = 0.012)., Conclusion: The addition of inflammatory markers increases the specificity of a clinical case definition for viral infection, particularly picornavirus infection.

Background: One of the public health challenges during an influenza pandemic is how to rapidly access groups of high-risk individuals to ensure that they have accurate information regarding prevention and management of infection. The aim of this survey was to evaluate the level of understanding of the H1N1-09 (Swine Flu) pandemic, amongst a high-risk group of individuals with chronic lung disease. This study was conducted in Melbourne, Australia towards the end of the 2009 pandemic., Methods: Questions included in the survey were based on the consumer information sheets available from the Department of Health (Victoria) website (frequently asked questions for the general public). Participants were recruited from patients attending community-based programs for chronic lung disease., Results: Eighty participants were interviewed in August-September 2009, the majority 70/80 were aware of the H1N1-09 pandemic in Melbourne. Most participants gained their information from media reports rather than health care providers. Although they were aware of some ways to decrease the spread of infection, only 20/80 (25%) knew that there were antiviral treatments available if they did contract the infection. It is noteworthy that in a substantial minority (25%), information reported in the media caused some confusion or anxiety and it appears that there was a gap in the provision of evidence-based information to this high-risk group., Conclusion: In the context of future pandemics, respiratory-outreach nurses and educators could be used to promote pertinent information regarding infection prevention and management to high-risk individuals. Currently this appeared to be an under-utilised means of imparting pandemic information to consumers.

Rationale: Much of the total disease burden and cost of chronic obstructive pulmonary disease (COPD) is associated with acute exacerbations of COPD (AECOPD). Serum amyloid A (SAA) is a novel candidate exacerbation biomarker identified by proteomic screening., Objectives: To assess SAA as a biomarker of AECOPD., Methods: Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) and (2) longitudinally with repeated measures (baseline vs. AECOPD vs. convalescence; 78 episodes in 37 individuals). Event severity was graded (I, ambulatory; II, hospitalized; III, respiratory failure) based on consensus guidelines., Measurements and Main Results: Presumptively newly acquired pathogens were associated with onset of symptomatic AECOPD. In the cross-sectional study, both SAA and C-reactive protein (CRP) were elevated at AECOPD onset compared with stable disease (SAA median, 7.7 vs. 57.6 mg/L; P < 0.01; CRP median, 4.6 vs. 12.5 mg/L; P < 0.01). Receiver operator characteristics analysis was used to generate area-under-curve values for event severity. SAA discriminated level II/III events (SAA, 0.88; 95% confidence interval, 0.80-0.94 vs. CRP, 0.80; 95% confidence interval, 0.70-0.87; P = 0.05). Combining SAA or CRP with major symptoms (Anthonisen criteria, dyspnea) did not further improve the prediction model for severe episodes. IL-6 and procalcitonin were not informative., Conclusions: SAA is a novel blood biomarker of AECOPD that is more sensitive than CRP alone or in combination with dyspnea. SAA may offer new insights into the pathogenesis of AECOPD.

Respiratory viruses are associated with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) in hospitalized patients. However, exacerbations are increasingly managed in the community, where the role of viruses is unclear. In community exacerbations, the causal association between viruses and exacerbation maybe confounded by random fluctuations in the prevalence of circulating respiratory viruses. Therefore, to determine whether viral respiratory tract infections are causally associated with community exacerbations, a time-matched case-control study was performed. Ninety-two subjects (mean age 72 yrs), with moderate to severe COPD, (mean FEV(1) 40% predicted), were enrolled. Nasopharyngeal swabs for viral multiplex polymerase chain reaction and atypical pneumonia serology were obtained at exacerbation onset. Control samples were collected in synchrony, from a randomly selected stable patient drawn from the same cohort. In 99 weeks of surveillance, there were 148 exacerbations. Odds of viral isolation were 11 times higher in cases, than their time-matched controls (34 discordant case-control pairs; in 31 pairs only the case had virus and in three pairs only control). Picornavirus (26), influenza A (3), parainfluenza 1,2,3 (2), respiratory syncytial virus (1), and adenovirus (1) were detected in cases while adenovirus (1) and picornavirus (2) were detected in controls. In patients with moderate or severe COPD the presence of a virus in upper airway secretions is strongly associated with the development of COPD exacerbations. These data support the causative role of viruses in triggering COPD exacerbations in the community.

Objective: To elucidate oxygen administration practices in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) and compare these practices with those recommended in internationally accepted guidelines., Design: Retrospective audit., Participants and Setting: 65 patients admitted to a Melbourne university teaching hospital via the emergency department (ED), identified through medical records by a discharge diagnosis (discharged between 1 June and 30 September 2005) of acute exacerbation of COPD (AECOPD). Those included had respiratory function test results consistent with British Thoracic Society guidelines for the diagnosis of COPD., Main Outcome Measures: Length of stay, need for high dependency unit (HDU) admission, use of non-invasive ventilation (NIV), and use of arterial blood gas (ABG) tests., Results: Our audit showed that 95% of patients defined as retaining carbon dioxide received oxygen at a flow rate greater than 2 L/min. This process began in the ambulance and continued in the ED, often without monitoring of ABG levels. Length of stay was significantly longer (P = 0.029); need for NIV on admission greater (P = 0.0124); and rate of admission to the HDU higher (P = 0.0124) in patients who achieved a partial pressure of arterial oxygen (PaO(2)) >/= 74.5 mmHg compared with those with a PaO(2) < 74.5 mmHg., Conclusions: The vast majority of patients with AECOPD presenting to our university teaching hospital receive oxygen therapy outside of internationally accepted guidelines, often without monitoring of ABG levels. The use of high-flow oxygen may contribute to an increased length of stay, more frequent admission to HDU and greater use of NIV among patients who achieve a higher PaO(2).