J R Hurst

Airway and systemic inflammation and decline in lung function in patients with COPD.

n n Study objectivesn Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.n n n Patients and designn A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).n n n Resultsn During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.n n n Conclusionsn In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.n n

Inflammatory changes, recovery and recurrence at COPD exacerbation

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35u2005days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8u2005mg·L−1 versus 3.4u2005mg·L−1. Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.

Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD.

n n Study objectivesn The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.n n n Designn Prospective cohort study.n n n Settingn Outpatient Department, London Chest Hospital, London, UK.n n n Patientsn Thirty-nine patients with COPD.n n n Measurementsn We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.n n n Resultsn A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.n n n Conclusionsn The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.n n

Relationships Among Bacteria, Upper Airway, Lower Airway, and Systemic Inflammation in COPD

STUDY OBJECTIVEnThe upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response.nnnDESIGNnProspective cohort study.nnnSETTINGnOutpatient Department, London Chest Hospital, London, UK.nnnPARTICIPANTSnForty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status.nnnMEASUREMENTSnSerum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects.nnnRESULTSnCOPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response.nnnCONCLUSIONSnCOPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.

Epidemiological relationships between the common cold and exacerbation frequency in COPD.

Higher exacerbation incidence rates in chronic obstructive pulmonary disease (COPD) are associated with more rapid decline in lung function and poorer quality of life, yet the mechanisms determining susceptibility to exacerbation remain ill-defined. The same viruses responsible for common colds are frequently isolated during exacerbations. The current authors hypothesised that exacerbation frequency may be associated with an increased frequency of colds, and investigated whether increased exacerbation frequency was associated with increased acquisition of colds, or a greater likelihood of exacerbation once a cold has been acquired. A total of 150 patients with COPD completed diary cards recording peak expiratory flow, and respiratory and coryzal symptoms for a median 1,047 days. Annual cold and exacerbation incidence rates (cold and exacerbation frequency) were calculated, and the relationships between these variables were investigated. This analysis is based on 1,005 colds and 1,493 exacerbations. Frequent exacerbators (i.e. those whose exacerbation frequency was greater than the median) experienced significantly more colds than infrequent exacerbators (1.73 versus 0.94·yr−1). The likelihood of exacerbation during a cold was unaffected by exacerbation frequency. Patients experiencing frequent colds had a significantly higher exposure to cigarette smoke (46 versus 33 pack-yrs). Exacerbation frequency in chronic obstructive pulmonary disease is associated with an increased frequency of acquiring the common cold, rather than an increased propensity to exacerbation once a cold has been acquired.

Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation

Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions.

Nasal symptoms, airway obstruction and disease severity in chronic obstructive pulmonary disease.

Background:u2002 Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the lung in association with airflow obstruction. There is increasing evidence of upper airway involvement in COPD and we have reported that this nasal inflammation is proportional to that in the lung. Given recognized relationships between lower airway inflammation and spirometric indices such as the Forced Expiratory Volume in one second (FEV1), we hypothesized that there may be a relationship between nasal obstruction and FEV1 in COPD. We also sought to investigate relationships between nasal symptoms and nasal patency in COPD.

Chronic obstructive pulmonary disease exacerbation and risk of pulmonary embolism

Pulmonary embolism is not a common feature in patients with chronic obstructive pulmonary disease with uncomplicated exacerbations.

Reviewer selection: author or editor knows best?

Differential behaviour of author and editor suggested reviewersnnT horax is now the second highest ranked respiratory journal and submissions are increasing year on year.1 To attract high quality manuscripts, authors must have confidence in our editorial process and we are committed to continuing and improving the transparency, efficiency, and fairness of peer review.nnWhen the current Editors took over the journal in 2003, Thorax changed to online manuscript submission2 and, for the first time, authors were formally invited to suggest up to four suitable peer reviewers for their work. Indeed, we encourage authors to suggest reviewers, as set out in our advice to contributors.3 Peer review is a vital step in the editorial process, guiding the selection of appropriate papers for publication and providing constructive comments for authors to improve their work. So, …

S115 Hot-hmv uk trial secondary outcome analysis: early readmission is reduced by the addition of home mechanical ventilation to home oxygen therapy in copd patients with chronic respiratory failure following a life-threatening exacerbation

Introduction Hospital readmission following treatment for a life-threatening exacerbation of COPD with acute NIV is frequent and associated with an adverse impact in terms of lung function and health related quality of life. They have been identified as a priority area in the NHS with financial penalties for any patient readmitted within 28 days following discharge. Method A multicentre open labelled randomised controlled trial recruited patients with persistent hypercapnia (PaCO2 > 7 kPa) 2–4 weeks following resolution of acute acidosis. Patients were randomised to either home oxygen therapy (HOT) or HOT and home mechanical ventilation (HOT-HMV). HMV was titrated overnight to control nocturnal hypercapnia. Follow up was for 12 months. The primary outcome, 12-month admission free survival, has been reported previously demonstrating a significant treatment effect (ERS 2016). Secondary outcome analysis included 28-day all-cause hospital readmission and 12 month exacerbation rate. Results 116 patients were randomised (HOT = 59, HOT-HMV = 57), age 67 ± 10 years, FEV1 0.6 ± 0.2 L, PaCO2 7.9 ± 0.9 kPa. 28-day readmission was 22 (37%) in the HOT and 7 (12%) in the HOT-HMV arm (unadjusted HR 0.27, 0.12 to 0.63, p = 0.003; adjusted HR 0.26, 0.11 to 0.61, p = 0.002) (Figure 1). 12 month exacerbation rate was reduced from median 5 (1 to 9) per year in the HOT arm to 4 (2to 6) in the HOT-HMV arm (unadjusted HR 0.64 (0.44 to 0.94); p = 0.022; adjusted HR 0.66, 0.46 to 0.95, p = 0.026). Conclusion The addition of HMV to HOT in patients with persistent hypercapnia following an acute life-threatening exacerbation of COPD reduces both 28-day readmission and 12 month exacerbation frequency. These data strongly support a change in clinical practice in the management of patients with severe COPD and persistent hypercapnia. Abstract S115 Figure 1 Time to hospital re-admission by treatment arm